Open AccessGenomic absence of the gene encoding T cell receptor V β 7.2 is linked to the presence of autoantibodies in Sjögren's syndrome
Author(s) -
Manavalan Sanil J.,
Valiando Jennifer R.,
Reeves Westley H.,
Arnett Frank C.,
Necker Antje,
Simantov Ronit,
Lyons Robert,
Satoh Minoru,
Posnett David N.
Publication year - 2004
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.11429
Subject(s) - t cell receptor , biology , genotype , t cell , gene , haplotype , autoantibody , locus (genetics) , allele , microbiology and biotechnology , genotyping , genetics , antibody , immunology , immune system
Objective It is not yet known whether the absence of certain T cell receptor V β (TCRBV) genes (e.g., due to genomic deletion) has functional significance. We examined this question in relation to a known 21.6‐kb insertion/deletion‐related polymorphism (IDRP) in the human BV locus. Methods New polymerase chain reaction (PCR) genotyping methods were used. Monoclonal antibodies to TCRBV gene products were used to confirm the absence of the relevant proteins. Patients with Sjögren's syndrome (SS) or systemic lupus erythematosus (SLE) were compared with normal controls with regard to TCR genotypes and serologic profiles. Results There are 3 known haplotypes (I, D1, D2) and 6 possible genotypes related to the 21.6‐kb IDRP. Novel PCR‐based methods were used to define these genotypes. In subjects with deleted/deleted (D/D) genotypes, T cells could not express V β 7.2 TCRs, as assayed with a new antibody specific for V β 7.2. This was the sole significant difference between subjects without the insertion and those with either 1 or 2 copies. Surprisingly, we found that the D/D genotype was associated with primary SS, but only when pathogenic autoantibodies were present. Conclusion These results suggest that T cells expressing TCRs with V β 7.2 are protective against a pathogenic immune response in SS. Thus, genomic polymorphism of TCR genes (along with the correct HLA alleles) determines whether T cells can direct a pathogenic autoimmune response.