What is the main difference between human leukocyte antigen (HLA) and major histocompatibility complex (MHC)?

HLA vs MHC: Nomenclature Distinction

HLA (Human Leukocyte Antigen) is simply the human-specific name for MHC (Major Histocompatibility Complex)—they refer to the same genetic system, with MHC being the general term used across species and HLA being the term specifically applied to humans. 1

Key Conceptual Framework

Terminology Hierarchy

• MHC is the broader, species-agnostic term that describes the genetic complex responsible for encoding molecules involved in antigen presentation across all vertebrates 1
• HLA is the human-specific designation for this same genetic system, located on chromosome 6p21.3 1, 2, 3
• The terms are used interchangeably when discussing human immunology, though "MHC" often appears in comparative immunology or when discussing the molecular complexes themselves, while "HLA" is used when referring to the specific human genes and alleles 1

Genomic Organization

• The MHC/HLA region spans approximately 4,000 kb on chromosome 6 and contains over 200 genes, including both HLA genes and non-HLA genes 1, 2
• The region is divided into three subclasses 1:
  • Class I region (~2,000 kb): includes HLA-A, HLA-B, HLA-C genes 1, 2
  • Class II region (~1,000 kb): includes HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1, and related genes 1
  • Class III region: contains complement genes (C2, C4, Bf) and other immune-related genes 1, 2

Functional Context

Protein Products

• MHC class I molecules (encoded by HLA-A, -B, -C genes) are expressed on nearly all nucleated cells and present intracellular peptides to CD8+ T cells 1
• MHC class II molecules (encoded by HLA-DR, -DQ, -DP genes) are expressed primarily on antigen-presenting cells and present extracellular peptides to CD4+ T cells 1

Clinical Relevance

• In clinical practice, "HLA typing" refers to determining a patient's specific alleles at HLA loci for transplantation matching or disease risk assessment 1, 4
• The HLA region has the largest number of disease associations of any genomic locus, particularly for autoimmune conditions 1, 4
• HLA-DRB1 alleles are strongly associated with type 1 diabetes, rheumatoid arthritis, and autoimmune hepatitis, though routine typing is not recommended for clinical diagnosis 1, 4

Common Pitfall

• Do not confuse the genetic locus (HLA/MHC genes) with the protein products (MHC molecules): The genes are called HLA genes in humans, but the proteins they encode are often referred to as MHC class I or class II molecules in scientific literature 1