HLAs, TCRs, and KIRs, a Triumvirate of Human Cell-Mediated Immunity

Annu Rev Biochem. 2020 Jun 20:89:717-739. doi: 10.1146/annurev-biochem-011520-102754.

Abstract

In all human cells, human leukocyte antigen (HLA) class I glycoproteins assemble with a peptide and take it to the cell surface for surveillance by lymphocytes. These include natural killer (NK) cells and γδ T cells of innate immunity and αβ T cells of adaptive immunity. In healthy cells, the presented peptides derive from human proteins, to which lymphocytes are tolerant. In pathogen-infected cells, HLA class I expression is perturbed. Reduced HLA class I expression is detected by KIR and CD94:NKG2A receptors of NK cells. Almost any change in peptide presentation can be detected by αβ CD8+ T cells. In responding to extracellular pathogens, HLA class II glycoproteins, expressed by specialized antigen-presenting cells, present peptides to αβ CD4+ T cells. In comparison to the families of major histocompatibility complex (MHC) class I, MHC class II and αβ T cell receptors, the antigenic specificity of the γδ T cell receptors is incompletely understood.

Keywords: HLA; KIR; TCR; haplotype; lymphocyte; polymorphism.

Publication types

  • Review

MeSH terms

  • Antigen Presentation
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Evolution, Molecular
  • Gene Expression Regulation
  • Haplotypes
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / classification
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / chemistry*
  • Histocompatibility Antigens Class II / classification
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunity, Cellular*
  • Immunity, Innate
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Models, Molecular
  • NK Cell Lectin-Like Receptor Subfamily D / chemistry*
  • NK Cell Lectin-Like Receptor Subfamily D / genetics
  • NK Cell Lectin-Like Receptor Subfamily D / immunology
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / chemistry*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, KIR / chemistry*
  • Receptors, KIR / classification
  • Receptors, KIR / genetics
  • Receptors, KIR / immunology
  • Signal Transduction

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • KLRD1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, KIR