Incompatibility for or pre-immunization against M1s determinants decreases lethal graft-versus-host reaction developed across non-H-2 and/or H-2 barriers

The effect of incompatibility for M1s determinants was studied in lethal graft-versus-host reaction (GVHR) in the mouse. GVHR was induced in adult recipients of the following H-2k strains: (AKR x B10.BR)F1 (Mlsa/Mlsb); (C3H x B10.BR)F1 (Mlsc/Mlsb); (CBA/J x B10.BR)F1 (Mlsd/Mlsb) and (CBA/H x B10. BR)F1 (Mlsb). Recipient mice were heavily irradiated and grafted with bone marrow and spleen cells from H-2 compatible B10.BR (H-2k, Mlsb) or H-2 incompatible B10.D2 (H-2d, Mlsb) or B10 (H-2b, Mlsb) strains. The cells from B10.D2 and B10 donors were normal, while those from B10.BR donors were either normal or pre-immunized against the recipient strains. In all experiments the survival of recipients with Mlsa/Mlsb and Mlsd/Mlsb phenotypes, and only in one experiment of those with Mlsc/Mlsb phenotype was greater and/or the survival time longer than that of recipients expressing only Mlsb. However, late deaths (greater than 120 days post grafting) observed after grafting of normal B10.BR cells were more frequent in Mlsd/Mlsb than in Mlsb strains. On the other hand, when B10.BR donor cells were pre-immunized against H-2k compatible (AKR x B10.BR)F1 (Mlsa/Mlsb) or (CBA/J x B10.BR)F1 (Mlsd/Mlsb) strains, the survival time of H-2 incompatible (B10 x B10.BR)F1 (H-2b/k, Mlsb) recipients was longer than when donor cells were pre-immunized against (CBA/H x B10-BR)F1 (Mlsb) strain. We conclude that donor incompatibility for Mlsa or Mlsd or donor-pre-immunization against Mlsa or Mlsd exerts a protective effect on lethal GVHR developed across non-H-2 or H-2 barriers; the protective effect of Mlsc is less efficient or absent. The Mls-induced protective effect shows the following properties: (a) efficiency in vivo correlates with the capacity of the corresponding alleles to stimulate an in vitro MLR; (b) is efficient in either primary or secondary response to other minor antigens; (c) is not H-2 restricted; (d) is nonspecific; (e) disappears late after grafting; (f) with respect to the genetic background, the early protective effect is followed, late after grafting, by an opposite effect which increases the mortality, suggesting that Mls locus determinants are capable of activating several cell populations with different biological functions.     

DIFFERENTIAL SUSCEPTIBILITY OF SPLEEN CELLS FROM C3H/HeN (H-2k) AND C3HfB/HeN (H-2kv1) MOUSE STRAINS TO CYTOTOXICITY BY MONOCLONAL ANTI-Kk ANTIBODY (CLONE 11-4)

Spleen cells from C3HfB/HeN mice (H-2^kv1) were markedly less susceptible to lysis by monoclonal anti-K^k antibody (Clone 11-4) than spleen cells from C3H/HeN mice (H-2^k). Less than 50% of C3HfB/HeN cells were lysed even at the highest antibody concentration tested compared to 70% of C3H/HeN cells. The difference in end point titre of the antibody tested on cells from the two strains was 5-10-fold. Similar differences were not observed using the conventional H-2K^k-typing antiserum (D-23).