H-2 Antigens pp 465-477 | Cite as

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

  • Louis A. Matis
  • Simona B. Sorger
  • Pamela J. Fink
  • David L. McElligot
  • Stephen M. Hedrick
Part of the NATO ASI Series book series (NSSA, volume 144)


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.

This analysis demonstrated definite correlations between sequence changes in particular regions of the TCR and functional specificity. A single Vα subfamily gene segment was predominantly expressed by all the B10.A T cell clones. In association with this Va gene, a limited set of Vβ genes were expressed, each correlating exactly with a unique response phenotype. A striking selection of both Jα and Jβ gene segments was also observed within each clonotype. Thus, Vα−Vβ combinatorial association, V-J combinatorial joining, and junctional diversity were shown to affect both antigen and MHC specificities of the cytochrome c-specific T cell clones. These represent the predominant mechanisms for the generation of diversity in the TCR repertoire.

In addition, the data revealed significant homologies between TCR that recognize Ia molecules as restriction elements in association with antigen and TCR that recognize the same Ia molecules as alloantigens. This suggests that MHC-restricted recognition and alloreactivity may simply reflect differences in the affinity of the interaction between the TCR and the MHC molecule.


Major Histocompatibility Complex Cell Clone Gene Segment Major Histocompatibility Complex Molecule Major Histocompatibility Complex Specificity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Louis A. Matis
    • 1
  • Simona B. Sorger
    • 2
  • Pamela J. Fink
    • 2
  • David L. McElligot
    • 2
  • Stephen M. Hedrick
    • 2
  1. 1.Molecular Immunology Laboratory, Division of Biochemistry and Biophysics, Center for Drugs and BiologicsFood and Drug AdministrationBethesdaUSA
  2. 2.Department of Biology and the Cancer CenterUniversity of CaliforniaSan Diego, La JollaUSA

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