DETERMINANT SELECTION FOR T-CELL TOLERANCE IN HEL-TRANSGENIC MICE - DISSOCIATION BETWEEN IMMUNOGENICITY AND TOLEROGENICITY

The induction of T-cell tolerance to self-antigens has been extensivel y characterized for immunodominant (ID) regions. However, tolerance to ward other minor self-determinants has received less attention, In the H-2(d) haplotype, HEL contains a single ID determinant (region 102-12 0) presented by I-E-d MHC class II molecules. The present study evalua tes the role of subdominant and cryptic HEL regions in maintaining tol erance. We have generated a mutated HEL antigen, HEL mu, whose ID regi on does not bind to I-E-d. Lymph node cells from HEL-immunized mice pr oliferated strongly to HEL mu in vitro. Two new stimulatory regions co mmon to HEL and HEL mu, were uncovered. They are produced during antig en processing and prime specific T lymphocytes, HEL-Tg mice were toler ant to these determinants, thus confirming their in vivo presentation. These HEL regions were as tolerogenic as the HEL ID determinant, desp ite their poor immunogenicity, These results demonstrate that there is not always a correlation between tolerogenicity and immunogenicity, a finding that may be critical for understanding T-cell tolerance. (C) 1997 Academic Press.