Molecular Analysis of Major Histocompatibility Complex (MHC) Molecule Recognition by the T Cell Receptor Alpha-Beta (α-β) Heterodimer

Abstract

We have examined the molecular basis of MHC-restricted antigen recognition and alloreactivity by the T cell receptor (TCR) α-β heterodimer in murine T cell clones specific for the peptide antigen pigeon cytochrome c. The T cell proliferative response to this antigen has been extensively characterized with regard to the fine specificity of both antigen and MHC molecule recognition. All T cell clones derived from B10.A strain mice share specificity for an antigenic determinant on the COOH-terminal peptide in association’ with the self E α k :E β k Ia molecule. However, distinct clonotypes can be identified based upon differences in the fine specificity of both antigen and MHC recognition, or concomitant alloreactivity. Structure-function analysis of TCR gene expression was performed by cDNA cloning and sequencing of productively rearranged α and β TCR genes from T cell clones representative of each clonotype, and by Southern blot analysis of a series of T cell clones of defined specificity using V segment probes derived from the cDNA clones.