2clv | pdb_00002clv
MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM8 PEPTIDE
Structural highlights
Function[HA1B_MOUSE] Involved in the presentation of foreign antigens to the immune system. [RBM5_MOUSE] Component of the spliceosome A complex. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron. May both positively and negatively regulate aopotosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes production of a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes production of a catalytically active form of CASP2/Caspase-2 that induces apoptosis (By similarity). [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe have characterized three different programs of activation for alloreactive CD8 T cells expressing the BM3.3 TCR, their elicitation depending on the characteristics of the stimulating peptide/MHC complex. The high-affinity interaction between the TCR and the K(b)-associated endogenous peptide pBM1 (INFDFNTI) induced a complete differentiation program into effector cells correlated with sustained ERK activation. The K(bm8) variant elicited a partial activation program with delayed T cell proliferation, poor CTL activity and undetectable ERK phosphorylation; this resulted from a low-avidity interaction of TCR BM3.3 with a newly identified endogenous peptide, pBM8 (SQYYYNSL). Interestingly, mismatched pBM1/K(bm8) complexes induced a split response in BM3.3 T cells, with total reconstitution of T cell proliferation but defective generation of CTL activity that was correlated with strong but shortened ERK phosphorylation. Crystal structures highlight the molecular basis for the higher stability of pBM8/K(bm8) compared to pBM1/K(bm8) complexes that exist in two conformers. This study illustrates the importance of the stability of both peptide/MHC and peptide/MHC-TCR interactions for induction of sustained signaling required to induce optimal CTL effector functions. Subtle allelic structural variations, amplified by peptide selection, may thus orient distinct outcomes of alloreactive TCR-based therapies. Distinct orientation of the alloreactive monoclonal CD8 T cell activation program by three different peptide/MHC complexes.,Auphan-Anezin N, Mazza C, Guimezanes A, Barrett-Wilt GA, Montero-Julian F, Roussel A, Hunt DF, Malissen B, Schmitt-Verhulst AM Eur J Immunol. 2006 Jul;36(7):1856-66. PMID:16761314[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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