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

We have previously described epltopes of the 18 kDa protein of Mycobacterium leprae which stimulate T and B cell responses in different strains of mice. A series of overlapping 20-mer peptides that span the 18 kDa protein were used as immunogens to examine T and B cell recognition of different epltopes. Strain-specific variation in the epltopes which induce the strongest responses was affected by genes linked to the H-2 complex and the T cell responses revealed by re-challenge with antigen were at least partially controlled by factors other than T cell specificity. We have examined the responses to one such antigen, peptlde 1–20, which contains strongly immunogenlc epltopes for T and B cells. T cells from draining lymph nodes of peptlde 1–20 immunized B10.BR, but not BALB/c mice, proliferated In vitro In response to rechallenge with peptlde 1–20 or whole protein. Immunization with the same peptlde also induced specific antibody only in B10.BR mice. However, Immunization of BALB/c mice results in ‘silent’ priming of T cells since these can be induced to respond In vitro to this antigen when cultured with activated macrophages as antigen presenting cells (APC). The failure of APC from mBALB/c mice primed with peptlde 1–20 to stimulate CD4+ proliferation when re-challenged In vitro and the failure to elicit antibody responses to peptlde 1–20 are presumably due to the same defect in antigen-presenting cell function, since presentation of peptlde 1–20 by activated macrophages is sufficient to restore both responses. The failure of APC to stimulate responses to this antigen in this model may be generally applicable to other cases of apparent non-responsiveness, and may have important implications for the understanding of T cell activation requirements.