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and an Antigenic Peptide Bound to MHC Class I1
Departments of
*
Cell Biology and
Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461
The interaction between TCRs and peptides presented by MHC
molecules determines the specificity of the T cell-mediated immune
response. To elucidate the biologically important structural features
of this interaction, we generated TCR 
-chain transgenic mice using a
TCR derived from a T cell clone specific for the immunodominant peptide
of vesicular stomatitis virus (RGYVYQGL, VSV8) presented by
H-2Kb. We immunized these mice with VSV8 or analogs
substituted at TCR contact residues (positions 1, 4, and 6) and
analyzed the CDR3
sequences of the elicited T cells. In
VSV8-specific CTLs, we observed a highly conserved residue at position
93 of CDR3 and preferred J usage, indicating that multiple
residues of CDR3 are critical for recognition of the peptide.
Certain substitutions at peptide position 4 induced changes at position
93 and in J usage, suggesting a potential interaction between
CDR3 and position 4. Cross-reactivity data revealed the foremost
importance of the J region in determining Ag specificity.
Surprisingly, substitution at position 6 of VSV8 to a negatively
charged residue induced a change at position 93 of CDR3 to a
positively charged residue, suggesting that CDR3 may interact with
position 6 in certain circumstances. Analogous interactions between the
TCR -chain and residues in the C-terminal half of the peptide have
not yet been revealed by the limited number of TCR/peptide-MHC crystal
structures reported to date. The transgenic mouse approach allows
hundreds of TCR/peptide-MHC interactions to be examined comparatively
easily, thus permitting a wide-ranging analysis of the possibilities
for Ag recognition in vivo.
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