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The molecular basis of allorecognition
1Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Annual Review of Immunology
|January 1, 1993
Summary
T cell recognition involves both MHC molecules and their peptide ligands. Differences in these peptides, not just MHC variations, significantly increase alloreactive cells.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Previously, T cell receptor recognition of allogeneic MHC molecules was thought to focus solely on polymorphic regions.
- This view has evolved with the understanding that T cell recognition is a complex interaction involving multiple molecular components.
Purpose of the Study:
- To review the evidence supporting the critical role of peptide ligands in T cell recognition of allogeneic MHC molecules.
- To explain how peptide differences amplify the impact of MHC polymorphism in allorecognition.
Main Methods:
- Literature review of studies investigating T cell receptor interactions with MHC molecules and peptide ligands.
- Analysis of experimental evidence demonstrating the influence of MHC-bound peptides on T cell selection and recognition.
Main Results:
- All T cell recognition, including self-tolerance and allorecognition, requires interaction with both the MHC molecule and its associated peptide.
- Polymorphic residues within the MHC peptide-binding groove, even if inaccessible to the T cell receptor, affect peptide selection.
- Differences in peptides presented by histoincompatible individuals significantly enhance the allogeneic response, leading to a high frequency of alloreactive T cells.
Conclusions:
- Peptide ligands are crucial determinants in T cell recognition of allogeneic MHC molecules.
- The interplay between MHC polymorphism and peptide variation is a key driver of alloreactivity.