Reversal of T cell unresponsiveness by augmentation of antigen presenting cell function.
We have previously described epitopes 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 epitopes. Strain-specific variation in the epitopes 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, peptide 1-20, which contains strongly immunogenic epitopes for T and B cells. T cells from draining lymph nodes of peptide 1-20 immunized B10.BR, but not BALB/c mice, proliferated in vitro in response to rechallenge with peptide 1-20 or whole protein. Immunization with the same peptide 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 peptide 1-20 to stimulate CD4+ proliferation when re-challenged in vitro and the failure to elicit antibody responses to peptide 1-20 are presumably due to the same defect in antigen-presenting cell function, since presentation of peptide 1-20 by activated macrophages is sufficient to restore both responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Doherty
T M
TM
Department of Immunology, DNAX Research Institute for Cellular and Molecular Biology, Palo Alto, CA 94040.
Love
S G
SG
Harding
D R
DR
Watson
J D
JD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D007114:Immunization; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009166:Mycobacterium leprae / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D010455:Peptides