DOMINANT AND CRYPTIC ANTIGENS IN THE MHC CLASS-I RESTRICTED T-CELL RESPONSE ACROSS A COMPLEX MINOR HISTOCOMPATIBILITY BARRIER - ANALYSIS AND MAPPING BY ELUTION OF CELLULAR PEPTIDES

T cell responses against complex antigens are often directed against a limited set of immunodominant determinants. We have studied this phen omenon at the level of cellularly processed peptides recognized by CTL in the B6 anti-BALB.B minor histocompatibility (H) barrier, comprisin g at least 29 antigen loci. B6 anti-BALB.B CTL always recognized three reverse phase HPLC fractions in BALB.B eluates, whether the latter we re obtained from cell lysates or immunoaffinity purified class I molec ules. One of these immunodominant epitopes (termed IDE-I) was H-2D(b) restricted, and two (termed IDE-2 and IDE-3) were H-2K(b) restricted. B6 mice were immunized with spleen cells from B6 congenic mice carryin g single minor H loci from BALB.B with the aim to assign IDE to given minor H loci and to investigate whether additional epitopes could be i dentified in the absence of the immunodominant ones. IDE-3 was found t o be associated to the locus H-28; in addition five so called cryptic epitopes were defined. Induction of CTL against these epitopes require d immunization with cells of the congenic strain; BALB.B spleen cells failed to immunize. One subgroup of these epitopes (those associated t o H-8, H-19 and H-25) were nevertheless found to be processed and load ed in class I molecules of BALB.B cells, while there was no evidence f or this for H-35 and H-36. For 10 additional congenic strains, no CTL response was detected. The results are discussed in relation to the ge netic and molecular basis of minor H antigens, and mechanisms for epit ope dominance operating at the level of the APC or responding T cells,