Rt. Carson et al., T-CELL RECEPTOR RECOGNITION OF MHC CLASS II-BOUND PEPTIDE FLANKING RESIDUES ENHANCES IMMUNOGENICITY AND RESULTS IN ALTERED TCR-V REGION USAGE, Immunity, 7(3), 1997, pp. 387-399
Naturally processed MHC class II-bound peptides possess ragged NH2 and
COOH termini. It is not known whether these peptide flanking residues
(PFRs), which lie outside the MHC anchor residues, are recognized by
the TCR or influence immunogenicity. Here we analyzed T cell responses
to the COOH-terminal PFR of the H-2A(k) immunodominant epitope of hen
egg lysozyme (HEL) 52-61. Surprisingly, the majority of T cells were
completely dependent on, and specific for, the COOH-terminal PFR of th
e immunogen. In addition, there were striking correlations between TCR
V beta usage and PFR dependence. We hypothesize that the V alpha CDR1
region recognizes NH2-terminal PFRs, while the V beta CDR1 region rec
ognizes COOH-terminal PFRs. Last, peptides containing PFRs were consid
erably more immunogenic and mediated a greater recall response to the
HEL protein. These results demonstrate that PFRs, which are a unique c
haracteristic of peptides bound to MHC class II molecules, can have a
profound effect on TCR recognition and T cell function. These data may
have important implications for peptide-based immunotherapy and vacci
ne development.