Paper I
Question
HLA antigens
Answer
HLA (Human Leukocyte Antigen) antigens are the human equivalent of the Major Histocompatibility Complex (MHC), cell-surface glycoproteins encoded by a highly polymorphic gene cluster on chromosome 6, central to antigen presentation and self/non-self discrimination.
Classes:
- HLA class I (HLA-A, -B, -C) — expressed on almost all nucleated cells; present endogenously processed peptides (e.g., viral proteins) to CD8+ cytotoxic T lymphocytes, enabling recognition and killing of infected/abnormal cells.
- HLA class II (HLA-DR, -DQ, -DP) — expressed mainly on professional antigen-presenting cells (dendritic cells, macrophages, B cells); present exogenously processed peptides to CD4+ helper T lymphocytes, initiating the adaptive immune response.
Functions/significance:
- Antigen presentation — the fundamental mechanism by which T cells recognize antigen, since T-cell receptors only recognize peptide bound within an MHC/HLA groove (MHC restriction).
- Transplantation — HLA matching between donor and recipient is critical for solid organ and haematopoietic stem cell transplantation; mismatch triggers graft rejection (via T-cell recognition of foreign HLA) and, in bone marrow transplant, graft-versus-host disease.
- Disease association — certain HLA alleles are strongly associated with specific autoimmune/inflammatory diseases (e.g., HLA-B27 with ankylosing spondylitis, HLA-DR3/DR4 with Type 1 diabetes and rheumatoid arthritis), useful diagnostically and reflecting the role of MHC in shaping susceptibility to autoimmunity.
- Paternity testing and forensic identification — HLA polymorphism is exploited for individual identification given its high degree of allelic variability between individuals.