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Publication Abstract from PubMed

Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vbeta8.1(+) precursors, which dictated susceptibility to cerebral malaria and conferred protection against recombinant Listeria monocytogenes infection. Structural analysis of a prototypical Vbeta8.1(+) TCR-H-2D(b)-GAP5040-48 ternary complex revealed that germline-encoded complementarity-determining region 1beta residues present exclusively in the Vbeta8.1 segment mediated essential interactions with the GAP5040-48 peptide. Collectively, these findings demonstrated that Vbeta8.1 functioned as an Ir gene that was indispensable for immune reactivity against the malaria GAP5040-48 epitope.

A T Cell Receptor Locus Harbors a Malaria-Specific Immune Response Gene.,Van Braeckel-Budimir N, Gras S, Ladell K, Josephs TM, Pewe L, Urban SL, Miners KL, Farenc C, Price DA, Rossjohn J, Harty JT Immunity. 2017 Nov 21;47(5):835-847.e4. doi: 10.1016/j.immuni.2017.10.013. Epub, 2017 Nov 14. PMID:29150238^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.