Biochemical variation of human Ia like antigens detected with monoclonal antibodies

Four mouse monoclonal antibodies to human B cell surface determinants previously described as being directed against Ia like (MHC class II) antigens, have been shown to precipitate Ia alpha and beta chains. Electrophoretic transfer experiments showed one antibody to be directed against Ia alpha chains and two others to be against Ia beta chains. The antibodies were then used to analyse a range of cell types and a large number of lymphoblastoid and lymphoma cell lines. Ia antigens could not be detected on peripheral blood T cells, cord endothelium or T cell lines but their presence was confirmed on activated T cells and peripheral blood non-T cells. There was both qualitative and quantitative variation of Ia like antigen expression on B cell lines, including an apparent genetic polymorphism in alpha chain structure unrelated to DR allotypes and a single instance of a beta chain of abnormally high molecular weight.     

Distribution of Human Leukocyte Antigen-ABC and -D/DR Antigens in the Unfixed Human Testis

ABSTRACT: The distribution of the major histocompatibility complex (MHC) antigens in the unfixed human testicle was studied by indirect immunofluorescence. Three murine monoclonal antibodies to the common determinants of class I MHC antigens (human leukocyte antigen [HLA]-ABC) and three against class II MHC antigens (HLA-D/DR antigens), respectively, were utilized. No class I MHC antigens were identified on developing testicular germ cells including spermatozoa, but interstitial cells between the seminiferous tubules (including Leydig cells) and blood vessel endothelium expressed the antigen. Class II MHC antigens were not found on any cells within the seminiferous tubules. However, the class II antigen was identified on dendritic-like cells between the seminiferous tubules and on vessel endothelium, although its expression was expectedly limited. These findings indicate that human testicular germ cells express minimal or no MHC antigens.     

The role of MHC class II antigenic determinants in the function of human antigen binding T8+ cells, monocytes and helper and suppressor factors

The role of MHC class II antigens was investigated in the process of antigen binding by T8+ cells and monocytes (Mo) and in the functions of helper factor (HF) and suppressor factor (SF). Monoclonal antibodies (MoAbs) to HLA-DR, DC and SB determinants were used in immunofluorescence, inhibition of antigen binding and affinity chromatography of HF and SF. Indirect immunofluorescence studies suggest that T lymphocytes from peripheral blood of healthy subjects have a small proportion of cells expressing HLA-DR, beta chain determinants (1.4-3.8%). These belong predominantly to the T8+ subset of cells (4.6-8.8%), with only a very small proportion in the T4+ cells (0.1-1.8%). However, DC1 on DRw6+ T cells and SB2,3 on any HLA typed cells were found in significantly greater proportion than the DR antigens in both T8+ and T4+ cells, though this was again greater on T8+ (30 and 25%) than T4+ (8.3 and 14.4%) cells. Although Mo had a greatly increased proportion of cells with DR-beta chain determinants (27-45%) than the T8+ cells, the converse was found with DC1 and SB2,3 determinants (13.9 and 11.4%). Inhibition of 125I-streptococcal antigen (SA) binding to T8+ cells and to Mo by MoAbs to the class II antigens showed that DR-beta chain monomorphic or polymorphic antibodies and DC1 antibodies inhibited binding to both cell types by 66-94%. However, MoAbs to DR-alpha chains or to the SB2,3 determinant failed to yield significant inhibition. Affinity chromatography studies of HF and SF revealed that the DR-beta chain monomorphic and DC1 antibodies bound HF and SF activities and that this was not found with the DR-beta chain polymorphic or SB2,3 antibodies. The results of inhibition of 125I-SA binding to T8+ cells and Mo, and absorption of HF and SF by affinity chromatography with MoAbs suggest four categories of recognition of human MHC class II antigenic determinants. (1) Class II determinants shared by the T8+ cells, Mo, HF and SF and recognized by MoAbs to monomorphic beta chains (DA6.231) and to DC1. (2) Class II determinants shared only by the SA binding T8+ cells and Mo and recognized by the MoAbs to a polymorphic beta chain (DA6.164) and to a monomorphic DR determinant (OK.Ial). (3) Class II determinants shared only by the HF and SF and recognized by the MoAbs to one of the alpha chains (TAL.1B5). (4) Class II determinants not detected on the two cells or the two T cell factors.     

Sequential induction of MHC antigens on autochthonous cells of ileum affected by Crohn''s disease.

Changes were examined in the expression of Class I and II major histocompatibility complex (MHC) antigens by autochthonous cells of the terminal ileum affected by Crohn's disease. The study was based on the analysis of transmural specimens from terminal ileum segments obtained in the course of ileocolectomy for colon cancer and Crohn's disease. Serial sections were immunostained using monoclonal antibodies directed against monomorphic determinants of HLA-A,B,C, DR, DP, DQ, and the invariant chain (Ii) associated with Class II molecules. Compared with the normal state, the only change in Class I antigen expression occurring in Crohn's disease was the induction of HLA-A,B,C antigens in lymphatic endothelium. Changes in Class II antigen expression were more substantial. Enhancement of HLA-DR expression was found in enterocytes; DR induction was observed in glial cells of the visceral nervous plexus and in venular and venous endothelium. HLA-DP and DQ antigens were induced in enterocytes, glial cells, and capillary and venular endothelium, although this induction was restricted to areas of moderate or high inflammatory activity. The tissue distribution of Ii closely resembled that of HLA-DR, although this association was not strict: on the one hand, arterial endothelium contained low amounts of Ii in the absence of DR antigens; on the other hand, glial cells expressed Class II molecules in the absence of Ii. The extent of local enhancement/induction of MHC antigens was positively correlated with the local density of the cellular infiltrate. These data suggest that altered MHC antigen expression by autochthonous structures might be mediated by factors released from the lymphohistiocytic infiltrate, which is itself attracted by an unknown signal. In conjunction with an unknown antigen, the enhanced expression of Class II antigens might trigger an autoaggressive immune response.     

Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigens

Mutant human B-lymphoblastoid cell lines, 721.174 and 721.180, that have greatly reduced expressions of known class I and class II HLA antigens were produced by two cycles of gamma-ray mutagenesis followed by selection for HLA antigen loss. Residual binding of monoclonal antibodies directed against class II antigens was negligible except for 10% residual binding of SB-binding antibody ILR1. However, deletion of SB was functionally complete as indicated by failure of the mutants to stimulate proliferation of SB-primed lymphocytes. Residual binding of monoclonal antibodies directed against class I "framework" determinants was reduced by 90-95%. However, the binding of monoclonal antibodies directed against beta 2-microglobulin and against the A2 epitope recognized by monoclonal antibody BB 7.2 was about 20% of normal. The identities of the residual class I-like antigens are unknown. The mutants retained full expression of the EBV-induced EBVCS antigen. Mutants 721.174 and 721.180 have lost most, but definitely not all, of their capacity to stimulate primary allogeneic and autologous lymphoproliferative responses. Therefore, the mutants still express antigens other than those that are presently known to stimulate lymphocyte proliferation. By means of studies of the present sort, and in future studies on expression of transferred HLA genes, mutants 721.174 and 721.180 promise to be useful in molecular and functional analysis of MHC-region-encoded gene products and their genetic regulation.     

Expression of MHC class I determinants on erythrocytes of SLE patients

Strong expression of MHC Class I determinants had been observed on the erythrocytes of three genetically C4 deficient patients who all had SLE. In a study of 35 other SLE patients who were not C4 deficient, 30 showed a marked increase in the expression of MHC Class I on their erythrocytes. There was a correlation between the expression of erythrocyte Class I and disease activity. The polymorphic HLA determinants were detected by haemagglutination with human cytotoxic antisera from untransfused pregnant women. A shared monomorphic epitope of HLA-A, -B and -C, and beta 2-microglobulin were detected by haemagglutination with monoclonal antibodies. A monoclonal antibody for a monomorphic epitope on MHC Class II alpha and beta chains did not react. Erythrocytes from a group of RA patients and a group of normal controls had moderate and low expression respectively. We suggest that MHC Class I may be induced on erythrocytes maturing in a milieu containing mediators derived from activated cells of the immune system. Aberrant tissue expression of MHC antigens may be more widespread than has been previously recognized in diseases mediated by immune mechanisms.     

Early induction of MHC antigens in human liver grafts. An immunohistologic study.

The present study documents major histocompatibility complex (MHC) Class I and II expression during early acute rejection of human liver grafts. Serial graft biopsies (pretransplant, time zero, and 1 week) were studied. Ten patients received azathioprine (AZA) and prednisone; the other six patients were treated with quadruple therapy (azathioprine, cyclosporine A, prednisone, and cyclophosphamide). To study the specificity of changes in MHC antigen expression, biopsies of six patients with minor or no morphologic abnormalities served as controls. In addition, phenotypes of inflammatory cells present during rejection were analyzed using a panel of monoclonal antibodies. The results show that during acute rejection expression of MHC Class I and II antigens increased significantly in the AZA-treated patients, in a pattern similar to that seen in the patients treated with quadruple therapy, showing enhanced MHC Class I expression on hepatocytes, bile duct epithelium, and sinusoidal endothelium, and Class II antigen on Kupffer cells and sinusoidal endothelium. Bile duct epithelium was consistently positive for Class II antigen; no significant difference with the nonrejection group was observed. T cells are the predominant inflammatory cells during rejection with equal quantities of CD4+ and CD8+ cells. A majority of the infiltrating T cells show expression of Class II antigen but do not react with anti-interleukin-2 receptor antibody. This may be the result of immunosuppressive therapy or a simple reflection of the temporary expression of interleukin-2 receptors during lymphocyte activation. The authors hypothesize that the induction of MHC antigens on bile duct epithelium leads to rejection whereas the expression on hepatocytes represents an epiphenomenon.     

Clonal analysis of human T cell activation by the Mycoplasma arthritidis mitogen (MAS)

Mycoplasma arthritidis produces an as yet undefined soluble molecule (MAS) that has a potent mitogenic effect on T cells of several species. We have used cloned human cytotoxic and proliferative T lymphocytes to dissect the molecular mechanism of T cell activation by this mitogen. Reactivity to MAS is clonally expressed among T cell receptor (TcR) alpha/beta chain-expressing T cell clones of CD4+ or CD8+ phenotype, as well as CD4-8- TcR alpha/beta chain-negative T lymphocyte clones expressing the CD3-associated TcR gamma chain. MAS is able to induce cytotoxicity and/or proliferation in these T cell clones. For triggering of these T cells, regardless of their phenotype of specificity, the presence of autologous, allogeneic or xenogeneic major histocompatibility complex (MHC) class II molecules on accessory cells or target cells is necessary. However, T cells do not immunologically recognize MAS on class II molecules, since a direct action of MAS on the T cells themselves can be demonstrated. Triggering of T cells by MAS can be blocked by monoclonal antibodies against CD2, CD3 and the TcR alpha/beta chain dimer. We discuss as a possible explanation that MAS is a functionally bivalent molecule cross-linking TcR and MHC class II molecules. Thus, the mechanism of T cell activation by MAS has striking similarities to the mechanisms by which Staphylococcal enterotoxins activate T cells. It is intriguing that a similar mitogenic principle has been developed by two evolutionary distinct pathogenic microorganisms.     

Sheep lymphocyte antigens (OLA). I. Major histocompatibility complex class I molecules

Three monoclonal antibodies, SBU.I 41-17, 41-19 and 41-28, have been produced which recognize sheep Class I major histocompatibility complex antigens (OLA). All three antibodies are able to precipitate a heavy chain of 44,000 MW and a smaller beta 2-microglobulin of 12,000 MW from 125I-surface labelled lymphocytes. The antibodies have been used to localize OLA Class I antigens in lymphoid and non-lymphoid tissues using indirect immunoperoxidase histological staining and cytofluorograph analyses. Evidence suggests that the three antibodies are directed against monomorphic determinants but that they recognize different epitopes.     

Evolution of the MHC: antigenicity and unusual tissue distribution of Xenopus (frog) class II molecules

Antibodies that recognize Xenopus class II molecules have been developed. Mouse monoclonal antibodies were prepared by immunizing BALB/c mice with frog MHC antigens that had been partially purified with alloantisera, and by immunizing mouse spleen cells in vitro with activated Xenopus T lymphocytes. In addition, five mouse monoclonal antibodies specific for human class II antigens were found to cross-react with Xenopus class II antigens. A.TH mice, which do not express E class II molecules, always produce immunoprecipitating antibodies reactive with frog class II molecules after immunization with frog lymphocytes; other mouse strains rarely produce such antibodies. Two of the monoclonal antibodies raised against frog class II molecules recognize the denatured class II beta chain on Western blots, and the other three appear to recognize only the class II heterodimeric complex. The antibodies display differential reactivity with the allelic class II products of Xenopus. The monoclonal antibodies react with all adult lymphocytes in the spleen and peripheral blood, T cells and B cells having equivalent levels of class II antigens per cell. Class II molecules are "differentiation antigens" on adult thymocytes as the expression is greatest on the mature medullary population. The number of class II molecules/lymphocyte increases after culturing in medium containing fetal bovine serum. Sequential immunoprecipitation and isoelectric focusing experiments have shown that cell surface class II molecules immunoprecipitated with the monoclonal antibodies are the same as those immunoprecipitated with the cross-reactive antiserum specific for DR antigens which was previously used to identify frog class II molecules.     

Interactions of T lymphocytes with human vascular endothelial cells: role of endothelial cells surface antigens

We have studied the interactions of peripheral blood T lymphocytes with cultured human vascular endothelial cells, focusing upon endothelial cell surface antigens important for T cell recognition. Under standard culture conditions endothelial cells express class I but not class II major histocompatibility complex (MHC) antigens. However, class II antigens may be induced by activated T cells or T cell products, including the lymphokine immune interferon. Immune interferon concomitantly increases class I antigen expression and causes a change in cell shape. In addition to vascular endothelial cells, we have found that vascular smooth muscle cells and human dermal fibroblasts may also be induced by immune interferon to express class II antigens. All known human class II antigens are induced (i.e. HLA-DR, DC and SB) as is the associated invariant chain. Induced antigen expression in these cells is stable over several days, although mRNA levels decline rapidly upon withdrawal of interferon. Vascular and stromal cell class II antigens are functional, in that they can be recognized by cytolytic and helper T cell clones. Several non-MHC antigens are also involved in the recognition of endothelial and stromal cells by T cells. We propose a model for the role of inducible class II molecules on endothelium and stromal cells in vivo: The induction of class II MHC antigens on endothelial cells, locally mediated by activated T cells, enables endothelium to present an immunogenic cell surface structure, comprised of antigen plus self class II polymorphic determinants, which in turn, serves to recruit additional antigen-specific T cells from the circulation into the site of a developing cell mediated immune response. Class II molecules on stromal cells, also induced locally at the site of a developing response, confers immune accessory function on these cells and may serve to augment and sustain a T cell response.     

Murine monoclonal antibodies and human alloantisera specific for HLA inhibit monocyte phagocytosis of anti-D-sensitized human red blood cells

Evidence is presented that monoclonal antibodies (mAb) against some human major histocompatibility complex (MHC) gene products and human sera containing HLA antibodies strongly inhibit immune phagocytosis of anti-D-sensitized red blood cells by human monocytes. w6.32HL, a mAb against a monomorphic class I antigen of high cell surface density, revealed the strongest inhibition among mAb reactive with MHC class I products. mAb with preferential reactivity for monomorphic and polymorphic DR and DQ epitopes (L203, L227, IIIE3, Tü22, Genox 3.53 and IV12) were noninhibitory. Definite inhibition was also apparent with a mAb against DRw52/MT2 (I-LR2) and with an antibody to class II antigens of high cell surface density (2MC3). Human sera containing HLA antibodies showed strong inhibition of immune phagocytosis up to a dilution of 1/1000. This inhibition could not be abrogated by platelet absorption. This indicates that human sera inhibiting immune phagocytosis may comprise at least two types of antibodies: cytotoxic HLA-specific antibodies which may or may not be inhibitory, and inhibitory antibodies against monocytic antigens not necessarily cytotoxic. These latter antibodies may recognize HLA DR or another as yet undefined gene product within, or closely associated to, the human MHC.     

Phenotypic characterization and functional activity of human milk macrophages

A large population (about 80%) of the cells obtained from colostrum and early human milk were considered to be macrophages by the following criteria: nonspecific esterase stain, adherence, phagocytosis and IgG-Fc receptor expression. The majority of freshly isolated human milk macrophages (HMM phi) stain for the monocyte antigen OKM1. Another monocyte antigen, 61D3, was expressed only by 30% of HMM phi. Class II antigens were expressed by HMM phi. About 85% of the cells were DR-positive whereas 50% were DS-positive as assessed with a panel of monoclonal antibodies directed against class II antigens. Monocyte and class II antigens were gradually lost during in vitro culture. HMM phi can support proliferative response to antigens and mitogens when cocultured with autologous peripheral T cells. The proliferative response was significantly reduced when monoclonal antibodies to DR or DS were added to the assay. These results indicate that HMM phi have the phenotype and functional characteristics of antigen presenting cells.     

Differential expression and regulation of the human CD8α and CD8β chains

The CD8 glycoprotein is expressed by thymocytes, mature T cells and natural killer (NK) cells and has been implicated in the recognition of monomorphic determinants on major histocompatibility complex (MHC) Class I antigens, and in signal transduction during the course of T-cell activation. Both human and rodent CD8 antigens are comprised of two distinct polypeptide chains, alpha and beta. The majority of monoclonal antibodies (mAb) reactive with the human CD8 antigen bind the CD8 alpha chain, while a single mAb, T8/2T8-5H7, has been identified which binds to the CD8 alpha/beta heterodimer. While the two chains of CD8 have been presumed to be coordinately expressed in normal T cells, this is not always the case. Northern blot analysis of a panel of T-cell leukemias and normal cells demonstrate that CD8 alpha and CD8 beta are not invariably co-transcribed and phenotypic analysis of fresh and interleukin 2 (IL-2) expanded peripheral blood mononuclear cells (PBMC) confirm that the CD8 alpha and CD8 beta chains are differentially expressed at the cell surface. Four distinct subpopulations of CD8+ cells have been identified based on the expression of CD8 alpha/alpha or CD8 alpha/beta complexes: (1) T-cell receptor (TcR) alpha beta+ T cells which are CD8 alpha+/beta+; (2) TcR alpha beta+ T cells which are CD8 alpha+/beta-; (3) TcR gamma delta+ T cells which are CD8 alpha+/beta- and (4) natural killer (NK) cells which are CD8 alpha+/beta-. We also demonstrate the down-regulation of the CD8 alpha/beta heterodimers from the surface of a CD8+ T-cell clone following treatment with phorbol myristate acetate (PMA) while CD8 alpha/alpha homodimers remain on the cell surface. This observation demonstrates that a) a CD8+ T-cell clone can express both CD8 alpha/alpha homodimers and CD8 alpha/beta heterodimers and b) these two complexes do not have identical biological properties. Together, these data suggest that CD8 alpha/alpha and CD8 alpha/beta dimers may not subserve identical functions. The differential contribution of these two CD8 complexes should be considered in models of T-cell-mediated cytotoxicity and T-cell activation.     

Tumor cell membrane-bound heat shock protein 70 elicits antitumor immunity

B cell hybridomas expressing class I and II MHC molecules and producing antibodies directed against hemagglutinin protein of Rinderpest virus and human Mucin-1 have been used as surrogate B cells to study T cell responses against the antigens. The observed CTL and lymphoproliferative response indicates that anti-idiotypic B cells termed Jerne cells stimulate both T helper and T cytotoxic cells by virtue of their ability to present recycled or regurgitated peptido-mimics of antigen to T helper cells through class II MHC and de novo synthesized peptido-mimics of antigens to CTLs. Thus, T cell memory response can be perpetuated by anti-idiotypic Jerne B cells and these findings lend support to the earlier proposed relay hypothesis for perpetuation of immunological memory (IM).     

HLA antigens in ocular tissues. III. Antigen presentation by gamma interferon-treated cultured uveal cells

In previous studies we have shown that normal human uveal cells, with the exception of vascular endothelium, do not express class I or class II HLA antigens in vivo. Class I antigens are induced in vitro by a variety of cytokines, while class II antigens are only induced by gamma interferon. In this study we examine the capacity of cultured uveal cells, rendered class II HLA antigen positive by gamma interferon, to present antigen to T cells. Cultured uveal cells were found to present antigen (tetanus toxoid, PPD, and Candida albicans) to T cells, but only when they were pretreated with gamma interferon. This function of uveal cells was antigen specific and MHC restricted and was blocked by class II-specific monoclonal antibodies, indicating the crucial role of class II HLA antigens in antigen presentation.     

Engagement of major histocompatibility complex class I and class II molecules up-regulates intercellular adhesion of human B cells via a CD11/CD18-independent mechanism.

We have studied the role of major histocompatibility complex (MHC) molecules in the regulation of intercellular adhesion of human B cells. We found that molecules able to bind to MHC class II molecules, such as monoclonal antibodies or staphylococcal enterotoxins, induced rapid and sustained homotypic adhesion of Epstein-Barr virus (EBV)-transformed B cell lines as well as peripheral blood B lymphocytes. Moreover, anti-MHC class I monoclonal antibodies also stimulated intercellular adherence. Adhesion induced upon MHC engagement was faster and stronger than that triggered by phorbol esters. It needed active metabolism, but divalent cations were not required. Monoclonal antibodies directed against LFA-1 (CD11a/CD18) or its ligand ICAM-1 (CD54) did not inhibit MHC class II-induced homotypic adhesion of various EBV-transformed B cell lines, nor of a variant of the B cell line Raji expressing very low LFA-1 surface levels. Moreover, EBV-transformed B cells from a severe lymphocyte adhesion deficiency patient, lacking surface CD11/CD18, also aggregated in response to anti-MHC class I or class II monoclonal antibodies. Together these data indicate that engagement of MHC molecules may transduce signals to B cells resulting in up-regulation of intercellular adhesion, via an LFA-1-independent mechanism. This may play a role in the stabilization of T cell/antigen-presenting cell conjugates at the moment of antigen recognition.     

Sheep lymphocyte antigens (OLA). II. Major histocompatibility complex class II molecules

A panel of monoclonal antibodies have been produced which recognize monomorphic determinants of sheep MHC Class II antigens, including an allogenically derived murine monoclonal antibody specific for the I-E gene product. Immunoprecipitation and SDS-PAGE analyses indicates that these monoclonal antibodies recognize a non-covalently associated glycoprotein complex of molecular weight 30-32 kDa (alpha chain) and 24-26 kDa (beta chain). One and two colour immunofluorescence was used to measure the distribution of these 'Ia-like' antigens on mononuclear cells from various lymphoid organs. They were found almost exclusively on lymphocytes expressing surface immunoglobulin (B lymphocytes) and on a small population of surface immunoglobulin negative cells. Most thymocytes were negative for Class II molecules while thymic epithelial cells were positive. The tissue distribution of Class II molecules was found to be similar to that described in man. Individual monoclonal antibodies displayed no variations in reactivity with the different tissues studied.     

Major histocompatibility complex (MHC) restricted antigen recognition: high frequency of human T-cell clones recognizing novel MHC class II determinants

We have used antigen-specific human T-cell clones to study the relationship between MHC and antigen recognition specificities expressed by T cells. Tetanus toxoid (TT)-specific T-lymphocyte clones were derived from a immunized HLA-DR2,7 heterozygous donor by limiting dilution from peripheral blood mononuclear cells (PBM) restimulated with TT in vitro. Clones were screened for MHC-restricted antigen recognition against antigen-presenting cells (APC) from a panel of HLA-typed donors, using an in vitro T-cell proliferation assay. Several distinct patterns of antigen recognition were identified. In addition to T cells that recognized TT in association with donor class II MHC antigens, we found clones that simultaneously expressed self-restricted antigen recognition and alloreactivity, and clones with specificity for antigen in the context of MHC antigens not expressed by the T-cell donor. This was confirmed in inhibition studies using well-characterized monoclonal antibodies against class II MHC antigens to block specific proliferative responses. We propose a possible structure for the determinant recognized by two of the clones. These results suggest that the T-cell antigen receptor undergoes random or antigen-dependent changes in vitro, and that this may be a mechanism for somatic diversification of the T-cell repertoire.     

Polymyositis mediated by T lymphocytes that express the gamma/delta receptor.

BACKGROUND. The invasion and destruction of nonnecrotic muscle fibers by CD8+ cytotoxic T cells is considered a hallmark of polymyositis. In the cases of polymyositis reported so far, the autoinvasive CD8+ T cells expressed the common form of T-cell receptor for the recognition of antigen, the so-called alpha/beta T-cell receptor. We describe a 69-year-old man with polymyositis mediated by CD4-, CD8- T cells expressing the recently discovered, uncommon gamma/delta T-cell receptor. METHODS. We used immunofluorescence or immunoperoxidase techniques to study frozen sections of muscle from our patient, who had mild weakness of cervical and proximal limb muscles, and from control patients with polymyositis, inclusion-body myositis, dermatomyositis, or granulomatous myopathy with monoclonal antibodies against T-cell-related antigens (CD2, CD3, CD4, CD8, and gamma/delta T-cell receptor), B cells (CD22), major histocompatibility complex (MHC) and MHC-related antigens (MHC Class I, CD1a, CD1b, and CD1c), and the 65-kd heat-shock protein. The membrane contacts between the autoinvasive cells and the sarcolemma were investigated by electron microscopy. RESULTS. In the patient described here, but not in 28 others with inflammatory myopathies, myriad gamma/delta T cells surrounded and invaded nonnecrotic muscle fibers. All muscle fibers were highly reactive for MHC Class I antigen and the 65-kd heat-shock protein. Treatment with prednisone improved the clinical and histologic findings. CONCLUSIONS. Polymyositis can be mediated by gamma/delta T cells. This new form of polymyositis appears to be highly responsive to steroids.