Genomic absence of the gene encoding T cell receptor Vbeta7.2 is linked to the presence of autoantibodies in Sjögren's syndrome.
OBJECTIVE
It is not yet known whether the absence of certain T cell receptor V(beta) (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(beta)7.2 TCRs, as assayed with a new antibody specific for V(beta)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.


CONCLUSIONS
These results suggest that T cells expressing TCRs with V(beta)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.
Manavalan
Sanil J
SJ
Weill Medical College of Cornell University, New York, New York 10021, USA. dposnett@mail.med.cornell.edu
Valiando
Jennifer R
JR
Reeves
Westley H
WH
Arnett
Frank C
FC
Necker
Antje
A
Simantov
Ronit
R
Lyons
Robert
R
Satoh
Minoru
M
Posnett
David N
DN
D000974:Antibodies, Antinuclear / Q000276:immunology*; D001324:Autoantigens; D005260:Female; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D000097585:SS-B Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C035356:SS-A antibodies