| Summary: | Given the vast potential for diversification of the T cell receptor (TCR) repertoire and the fact that V ~ mice exist in the wild, it would have been predicted that in spite of the absence of 10 TCR. V ~ gene segments, V ~ mice would still have been able to produce an antigen-specific T cell response to all determinants. We have recently shown that V ~ mice, with a wild-type TCR Va repertoire, respond to peptide 110-121 of sperm whale myoglobin, with a majority of T cells expressing TCR V~8.2 and restricted to a hybrid I-AO/I-E d major histocompatibility complex molecule, and a smaller number of T cells expressing TCR Va8.1 and restricted to the I-A d molecule. However, V ~ mice, lacking members of the TCR V~8 gene family, responded only with I-Ad-restricted T cells. Thus, it appeared that the I-Ad-restricted response was less constrained, or more plastic. We now show that the two separate panels of I-Aa-restricted T cell hybrids derived from V ~ or V ~ mice in fact recognize distinct determinants within the same peptide 110-121. The determinant recognized by V ~ T ceils is NH2 terminal (core: 110-118) with an absolute requirement for the residue Ala-110 for a successful interaction with TCRs. On the other hand, V ~ T cells recognize the COOH-terminal region (core:112-118) on the same peptide with an absolute requirement for COOH-terminal residue 118. In the dominance hierarchy displayed
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