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      The HLA System: Genetics, Immunology, Clinical Testing, and Clinical Implications

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          Abstract

          The human major histocompatibility complex HLA is located on the short arm of chromosome 6. It is known to be the most polymorphic genetic system in humans. The biological role of the HLA class I and class II molecules is to present processed peptide antigens. The HLA system is clinically important as transplantation antigens. Molecular HLA allele typing is routinely performed to provide HLA class I and class II allele matching in unrelated donor hematopoietic stem cell transplantation. Prospective lymphocyte crossmatching is critical in solid organ transplantation to prevent allograft rejection. HLA alloimmunization causes various problems in transfusion therapy. The HLA system is associated with certain diseases, but its underlying mechanisms are not yet fully explained.

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          Most cited references71

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          Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1.

          The three-dimensional structure of the class II histocompatibility glycoprotein HLA-DR1 from human B-cell membranes has been determined by X-ray crystallography and is similar to that of class I HLA. Peptides are bound in an extended conformation that projects from both ends of an 'open-ended' antigen-binding groove. A prominent non-polar pocket into which an 'anchoring' peptide side chain fits is near one end of the binding groove. A dimer of the class II alpha beta heterodimers is seen in the crystal forms of HLA-DR1, suggesting class II HLA dimerization as a mechanism for initiating the cytoplasmic signalling events in T-cell activation.
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            Structure of the human class I histocompatibility antigen, HLA-A2.

            The class I histocompatibility antigen from human cell membranes has two structural motifs: the membrane-proximal end of the glycoprotein contains two domains with immunoglobulin-folds that are paired in a novel manner, and the region distal from the membrane is a platform of eight antiparallel beta-strands topped by alpha-helices. A large groove between the alpha-helices provides a binding site for processed foreign antigens. An unknown 'antigen' is found in this site in crystals of purified HLA-A2.
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              The HLA system. First of two parts.

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                Author and article information

                Journal
                Yonsei Med J
                YMJ
                Yonsei Medical Journal
                Yonsei University College of Medicine
                0513-5796
                1976-2437
                28 February 2007
                20 February 2007
                : 48
                : 1
                : 11-23
                Affiliations
                Department of Pathology, Mount Sinai School of Medicine, New York, NY, USA.
                Author notes
                Reprint address: requests to Dr. Sung Yoon Choo, Department of Pathology, Mount Sinai School of Medicine, One Gustave L. Levy Pl., Box 1024, New York, NY 10029, USA. Tel: 212-241-0839, Fax: 212-876-5994, yoon.choo@ 123456mountsinai.org
                Article
                10.3349/ymj.2007.48.1.11
                2628004
                17326240
                548230d9-49e2-4c7c-80d3-481d2c495dab
                Copyright © 2007 The Yonsei University College of Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 January 2007
                Categories
                Review Article

                Medicine
                transplantation,histocompatibility testing,hla,major histocompatibility complex
                Medicine
                transplantation, histocompatibility testing, hla, major histocompatibility complex

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