Reversal of T cell unresponsiveness by augmentation of antigen presenting cell function

We have previously described epltopes of the 18 kDa proteinof Mycobacterium leprae which stimulate T and B cell responsesin different strains of mice. A series of overlapping 20-merpeptides that span the 18 kDa protein were used as immunogensto examine T and B cell recognition of different epltopes. Strain-specificvariation in the epltopes which induce the strongest responseswas affected by genes linked to the H-2 complex and the T cellresponses revealed by re-challenge with antigen were at leastpartially controlled by factors other than T cell specificity.We have examined the responses to one such antigen, peptlde1–20, which contains strongly immunogenlc epltopes forT and B cells. T cells from draining lymph nodes of peptlde1–20 immunized B10.BR, but not BALB/c mice, proliferatedIn vitro In response to rechallenge with peptlde 1–20or whole protein. Immunization with the same peptlde also inducedspecific antibody only in B10.BR mice. However, Immunizationof BALB/c mice results in ‘silent’ priming of Tcells since these can be induced to respond In vitro to thisantigen when cultured with activated macrophages as antigenpresenting cells (APC). The failure of APC from mBALB/c miceprimed with peptlde 1–20 to stimulate CD4⁺ proliferationwhen re-challenged In vitro and the failure to elicit antibodyresponses to peptlde 1–20 are presumably due to the samedefect in antigen-presenting cell function, since presentationof peptlde 1–20 by activated macrophages is sufficientto restore both responses. The failure of APC to stimulate responsesto this antigen in this model may be generally applicable toother cases of apparent non-responsiveness, and may have importantimplications for the understanding of T cell activation requirements.