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TCRβ Chain That Forms Peptide-Independent Alloreactive TCR Transfers Reduced Reactivity with Irrelevant Peptide/MHC Complex
Journal article   Peer reviewed

TCRβ Chain That Forms Peptide-Independent Alloreactive TCR Transfers Reduced Reactivity with Irrelevant Peptide/MHC Complex

Fabio R Santori, Zoran Popmihajlov, Vladimir P Badovinac, Courtney Smith, Sasa Radoja, John T Harty and Stanislav Vukmanović
The Journal of immunology (1950), Vol.178(10), pp.6109-6114
05/15/2007
DOI: 10.4049/jimmunol.178.10.6109
PMID: 17475836

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Abstract

A major feature of the TCR repertoire is strong alloreactivity. Peptides presented by allogeneic MHC are irrelevant for recognition by a subset of alloreactive T cells. To characterize peptide-independent TCRs at the molecular level, we forced the expression of a TCRbeta chain isolated from a peptide-independent alloreactive CD8+ T cell line. The alloreactive TCR repertoire in the transgenic mouse was peptide dependent. However, analysis of essential TCR contacts formed during the recognition of self-MHC-restricted Ag showed that fewer contacts with peptide were established by the transgenic TCRbeta chain, and that this was compensated by additional contacts formed by endogenous TCRalpha chains. Thus, reduced interaction with the peptide appears to be a transferable feature of the peptide-independent TCRbeta chain. In addition, these findings demonstrate that reactivity to peptides is preferred over the reactivity to MHC during the formation of the TCR repertoire.
Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor - physiology Receptors, Antigen, T-Cell, alpha-beta - administration & dosage Ovalbumin - metabolism Lymphocyte Activation - genetics H-2 Antigens - genetics Receptors, Antigen, T-Cell, alpha-beta - biosynthesis CD8-Positive T-Lymphocytes - metabolism Peptide Fragments - genetics Peptide Fragments - metabolism H-2 Antigens - metabolism Mice, Inbred C57BL Peptide Fragments - administration & dosage Antigen Presentation - genetics Mice, Transgenic Peptide Fragments - biosynthesis Receptors, Antigen, T-Cell, alpha-beta - genetics Mice, Knockout beta 2-Microglobulin - deficiency H-2 Antigens - immunology Animals Cell Line, Tumor Mice Mice, Inbred BALB C Receptors, Antigen, T-Cell, alpha-beta - metabolism CD8-Positive T-Lymphocytes - immunology beta 2-Microglobulin - genetics

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