Allelic polymorphism in the T cell receptor and its impact on immune responses
نویسندگان
چکیده
In comparison to human leukocyte antigen (HLA) polymorphism, the impact of allelic sequence variation within T cell receptor (TCR) loci is much less understood. Particular TCR loci have been associated with autoimmunity, but the molecular basis for this phenomenon is undefined. We examined the T cell response to an HLA-B*3501-restricted epitope (HPVGEADYFEY) from Epstein-Barr virus (EBV), which is frequently dominated by a TRBV9*01(+) public TCR (TK3). However, the common allelic variant TRBV9*02, which differs by a single amino acid near the CDR2beta loop (Gln55-->His55), was never used in this response. The structure of the TK3 TCR, its allelic variant, and a nonnaturally occurring mutant (Gln55-->Ala55) in complex with HLA-B*3501(HPVGEADYFEY) revealed that the Gln55-->His55 polymorphism affected the charge complementarity at the TCR-peptide-MHC interface, resulting in reduced functional recognition of the cognate and naturally occurring variants of this EBV peptide. Thus, polymorphism in the TCR loci may contribute toward variability in immune responses and the outcome of infection.
منابع مشابه
The Association of Vitamin D Receptor Gene BsmI Polymorphism with Multiple Sclerosis in Iranian Patients
Background & Aims: 1,25-dihydroxyvitamin D3 (1,25 (OH)2 D3), the biologically active form of vitamin D, exerts an immunosuppressive effect through binding to its specific nuclear receptor. The present case-control study was done to examine the possible association of BsmI polymorphism in vitamin D receptor gene (VDR gene) with severity of multiple sclerosis (MS). Methods: 267 Iranian patients w...
متن کاملInvestigation of FcγRIIA and FcγRIIIA Polymorphism in Multiple Sclerosis: A Case Control Study
Background: Multiple Sclerosis (MS), the most common demyelinating disease of the CNS, is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of IgG (FcγR) might induce inflammatory responses through linking the humoral and cellular immune responses by targeting immune complexes to effector cells. Polymorphisms in some FcγR genes are associated with va...
متن کاملAllelic and Genotypic Distribution in Single Nucleotide Polymorphism (SNP) G.676A > G of Melanocortin-1 Receptor (MC1R) Gene in Indonesian Goat Breeds
The melanocortin-1 receptor (MC1R) gene has been investigated by many studies regarding the pigmentation variation in various species. In order to determine its allelic and genotypic distribution, we sequenced the goat MC1R gene from 78 individuals in ten populations (Gembrong, Senduro, Ettawa Grade, Boerawa, Boerka, Kosta, Samosir, Muara, Boer and Kacang). Direct sequencing m...
متن کاملPolymorphisms within Exon 9, But Not Intron 8, of the Vitamin D Receptor Gene Are Associated with Asthma
Objective(s) Deregulation of the immune system through allied factors and cytokine responses are thought to be important contributors to the pathogenesis of asthma. Vitamin D3 and its nuclear receptor appear to be factors that maybe involved in regulating immune responses during the progression of asthma. The aim of this study was to investigate the association between polymorphisms in intron ...
متن کاملP-202: StuI Polymorphism on the Androgen Receptor Gene in Women with Endometriosis
Background: Androgens have an anti-proliferative effect on endometrial cells. Human androgen receptor (AR) gene contains two polymorphic short tandem repeats of GGC and CAG, and a single-nucleotide polymorphism on exon 1 that is recognized by the restriction enzyme, StuI. Prior studies have shown that the lengths of the CAG and GGC repeats are inversely and linearly related to AR activity and a...
متن کامل