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.
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.
HUMAN LEUKOCYTE ANTIGENS (MAJOR HISTOCOMPATIBILITY COMPLEX)
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.
The two major classes of HLA antigens are homologous. However, there are areas of high variability ...