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The Journal of Immunology, Vol 146, Issue 10 3513-3522, Copyright © 1991 by American Association of Immunologists

ARTICLES

Amino acid residues in the T cell receptor CDR3 determine the antigenic reactivity patterns of insulin-reactive hybridomas

J Wither, J Pawling, L Phillips, T Delovitch and N Hozumi
Mount Sinai Research Institute, University of Toronto, Ontario, Canada.

We examined TCR gene usage in a panel of beef insulin/I-Ad-restricted T cell hybrids obtained from BALB/c mice. These hybrids demonstrated several distinct patterns of reactivity defined by their ability to respond to species variants of insulin. Correlation of TCR-alpha and - beta-gene usage with these patterns of reactivity demonstrated that TCR gene usage was restricted within Ag reactivity groups. In particular, V- J junctional regions (CDR3 equivalent) were restricted with conserved junctional amino acid motifs present in both TCR-alpha- and -beta- chains. Comparison of TCR gene usage in hybrids expressing identical V alpha and V beta gene segments but demonstrating different patterns of reactivity revealed that changes in either J alpha and/or J beta gene segment usage could alter antigenic reactivity. Indeed, single or limited amino acid differences within the CDR3 region were sufficient to markedly alter fine specificity. These data demonstrate the critical role for CDR3 in determining antigenic reactivity in beef insulin- reactive hybrids and are compatible with the current model of TCR/peptide/MHC interaction.


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A. Lim, L. Trautmann, M.-A. Peyrat, C. Couedel, F. Davodeau, F. Romagne, P. Kourilsky, and M. Bonneville
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J. E. Wither and B. Vukusic
The Orientation and Nature of the Interaction Between Beef Insulin-Specific TCRs and the Insulin/Class II MHC Complex
J. Immunol., February 15, 1999; 162(4): 2113 - 2122.
[Abstract] [Full Text] [PDF]


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