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INTRODUCTION

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SUMMARY

The human leukocyte antigens (HLAs) are highly polymorphic glycoproteins encoded by the major histocompatibility complex on chromosome 6. Their biologic function is presentation of antigenic peptides to T lymphocytes, and there are two major classes: class I (A, B, and C loci) and class II (DR, DQ, and DP loci). Class I antigens are present on almost all nucleated cells, whereas class II antigens are primarily expressed on B cells and other antigen-presenting cells such as dendritic cells, endothelial cells, and monocytes. These antigens play key roles in hematopoietic cell transplantation acceptance/rejection and allosensitization to nonleukoreduced blood transfusions leading to platelet transfusion refractoriness, with lesser, but distinct roles in solid-organ transplantation. Other clinically important lineage-specific white cell antigens include those on neutrophils, which are much less polymorphic and less commonly a cause of clinical problems than the HLA system. Antibody to neutrophil antigens plays a role in autoimmune neutropenia, and reactions such as transfusion-related acute lung injury. Platelets also possess a relatively limited number of polymorphic antigens that are involved in clinical problems such as posttransfusion purpura and platelet transfusion refractoriness, and neonatal problems such as alloimmune thrombocytopenia.

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Acronyms and Abbreviations

CDC, complement-dependent cytotoxicity; ELISA, enzyme-linked immunosorbent assay; GP, glycoprotein; GVHD, graft-versus-host disease; HLA, human leukocyte antigen; HNA, human neutrophil antigen; HPA, human platelet antigen; MHC, major histocompatibility complex; NAIT, neonatal alloimmune thrombocytopenia; NMDP, National Marrow Donor Program; PCR, polymerase chain reaction; PRA, panel reactive antibody; PTP, posttransfusion purpura; SSO, sequence-specific oligonucleotide; SSP, sequence-specific primer; TRALI, transfusion-related acute lung injury; WHO, World Health Organization.

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HUMAN LEUKOCYTE ANTIGENS (MAJOR HISTOCOMPATIBILITY COMPLEX)

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DEFINITION

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The human leukocyte antigens (HLAs) are highly polymorphic glycoproteins encoded by a region of genes known as the major histocompatibility complex (MHC) located on chromosome 6p21 and covering a region of approximately 7.6 Mbp.1,2 After ABO antigens, HLA antigens are the major barrier to transplantation. Their biologic function is to present antigenic peptides to T lymphocytes. The MHC codes for several groups of antigens. The best understood are the highly polymorphic, classical class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DR, HLA-DQ, and HLA-DP) antigens. Class I antigens are ubiquitous and present on most nucleated somatic cells. Class II antigens exhibit more restricted distribution, with varying levels of expression on B cells, dendritic cells, monocytes, macrophages, and endothelial cells. However, class II antigens can be induced on many cell types through activation.3 The nonclassical class Ib antigens HLA-E, HLA-F, and HLA-G, and the MHC class I chain-related antigens are much less polymorphic, their function less understood, and their tissue expression more limited. In addition the MHC region codes for a number of pseudogenes. This chapter focuses on the classic class I and II molecules because of their importance in transfusion and transplantation.

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The two major classes of HLA antigens are homologous. However, there are areas of high variability ...

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