3ft3
From Proteopedia
Crystal Structure of the minor histocompatibility peptide HA-1His in complex with HLA-A2
Structural highlights
Disease[B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.[1] Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Function[1A02_HUMAN] Involved in the presentation of foreign antigens to the immune system. [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe di-allelic HLA-A2 restricted minor histocompatibility Ag HA-1 locus codes for the highly immunogenic HA-1(His) and the nonimmunogenic HA-1(Arg) nonapeptides, differing in one amino acid. The HA-1(His) peptide is currently used for boosting the graft-vs-tumor responses after HLA matched HA-1 mismatched stem cell transplantation; usage of the HA-1(Arg) peptide would significantly enlarge the applicability for this therapy. Our studies on mechanisms causing the HA-1 unidirectional immunogenicity revealed marginal differences in proteasomal digestion, TAP translocation, and binding affinity, whereas both dissociation rates and structural analyses clearly showed marked differences in the stability of these two HLA-A2 bound alleles. These data provide a rationale for the lack of HA-1(Arg) peptide immunogenicity essential for the choice of tumor peptides for stem cell-based immunotherapeutic application. Steric hindrance and fast dissociation explain the lack of immunogenicity of the minor histocompatibility HA-1Arg Null allele.,Spierings E, Gras S, Reiser JB, Mommaas B, Almekinders M, Kester MG, Chouquet A, Le Gorrec M, Drijfhout JW, Ossendorp F, Housset D, Goulmy E J Immunol. 2009 Apr 15;182(8):4809-16. PMID:19342659[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations 10 reviews cite this structure No citations found See AlsoReferences
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Categories: Human | Large Structures | Chouquet, A | Gorrec, M Le | Goulmy, E | Gras, S | Housset, D | Reiser, J B | Spierings, E | Antigen presentation | Antigen processing | Graft rejection | Graft-versus-tumor immune system | Hla | Host-versus-graft disease | Human minor h antigen | Immune response | Immune system | Immunogenicity | Immunoglobulin domain | Membrane | Mhc i | Polymorphism | Transmembrane