Chapter 137: Human Leukocyte and Platelet Antigens

SUMMARY

The gene products of the major histocompatibility complex (MHC) in humans are designated human leukocyte antigens (HLAs) since they were first described as cell surface antigens of blood leukocytes. The HLA antigens are highly polymorphic glycoproteins encoded on the short arm of chromosome 6. There are three classes encoded in the HLA region: class I (A, B, and C loci), class II (DR, DQ, and DP loci), and class III (tumor necrosis factor, complement factor genes, etc). The biological function of class I and II antigens is to act as the gatekeepers to the human immune response by presenting antigenic peptides to T lymphocytes. Class I antigens are present on almost all nucleated cells, whereas class II antigens are primarily expressed on B cells (along with class I determinants) and other antigen-presenting cells such as dendritic cells, endothelial cells, and monocytes. These antigens and their associated antibodies play key roles in hematopoietic cell and solid organ transplantation compatibility. They are also intimately involved in allosensitization to nonleukoreduced blood components, leading to platelet transfusion refractoriness. 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 MHC system. Antibodies to neutrophil antigens play a role in alloimmune neonatal neutropenia, autoimmune neutropenia, and transfusion reactions such as transfusion-related acute lung injury. Platelets also possess a relatively limited number of platelet-specific polymorphic antigens that are involved in clinical disease states such as fetal/neonatal alloimmune thrombocytopenia, posttransfusion purpura, platelet transfusion refractoriness, and other alloimmune thrombocytopenias.

Acronyms and Abbreviations

AIN, alloimmune neutropenia; ANN, alloimmune neonatal neutropenia; ARD, antigen recognition domain; ARDS, acute respiratory distress syndrome; bp, base pair; BRM, biological response modifier; cPRA, calculated panel reactive antibodies; CDC, complement-dependent cytotoxicity; CTL2, choline transporter-like protein-2; ddNTPs, dideoxynucleotides; DSA, donor antigen specific antibodies; ELISA, enzyme-linked immunosorbent assay; epitope, a specific portion of an antigenic molecule to which an antibody attaches; FNAIT, fetal / neonatal alloimmune thrombocytopenia; GA, granulocyte agglutination; GIFT, granulocyte immunofluorescence testing; GP, glycoprotein; GPI, glycosylphosphatidylinositol; G-CSF, granulocyte-colony stimulating factor; GVHD, graft-versus-host disease; HIV, human immunodeficiency virus; HSCT, hematopoietic stem cell transplantation; HLA, human leukocyte antigen; HNA, human neutrophil antigen; HPA, human platelet antigen; MACE, modified antigen capture ELISA; MAGE, melanoma-associated gene; MAIPA, monoclonal antibody immobilization of platelet antigens; MAINA, monoclonal antibody immobilization of neutrophil antigens; Mbp, mega base pair; MFI, median fluorescent intensity; MHC, major histocompatibility complex; Mr, molecular mass; MUD, matched unrelated donors; NGS, next generation sequencing; NMDP, National Marrow Donor Program; PCR, polymerase chain reaction; PECAM-1, platelet endothelial cell adhesion molecule-1; PRA, panel reactive antibody; PTP, posttransfusion purpura; SBT, sequence-based typing; SNP, single nucleotide polymorphism; SSO, sequence-specific oligonucleotide; SSP, sequence-specific primer; TRAIN, transfusion-related alloimmune neutropenia; TRALI, transfusion-related acute lung injury; WHO, World Health Organization; xMHC, extended major histocompatibility complex.