1980 Nobel Prize in Physiology or Medicine
Reason for Award
for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions
Laureates
United States of America
France
United States of America
Explanation
Every cell in our body carries tiny name tags made of proteins. These tags are decided by our genes, so everyone’s pattern is different. Mr. Benacerraf, Mr. Dausset and Mr. Snell discovered that immune “guards,” our white blood cells, read these tags. The guards check the tag to decide whether a cell is friend or foe. When the tag is different, they may attack it as if it were a germ. Thanks to this finding, doctors can now match tags before organ transplants. The discovery also gives clues for making new medicines that help us fight diseases.
Related Keywords
Major Histocompatibility Complex
A gene cluster located on chromosome 6 in humans and chromosome 17 in mice that encodes proteins essential for self–non-self discrimination. It is divided into class I, class II and class III regions; class I and II molecules function as antigen presenters. The loci are extraordinarily polymorphic, with hundreds of alleles catalogued. They influence graft rejection, autoimmunity, infectious defense and tumor immunity. Comparative genomics indicates that balancing selection driven by pathogens maintains MHC diversity. The complex is a focal point in vaccine design and immunogenicity prediction.
HLA antigens
An abbreviation for Human Leukocyte Antigen, referring to human MHC molecules. Initially detected by leukocyte agglutination assays, they are now typed with high precision by molecular genetics. HLA-A, ‑B, ‑C are class I, whereas HLA-DR, ‑DP and ‑DQ belong to class II; allele matching between donor and recipient is crucial for reducing transplant rejection. HLA variants strongly influence susceptibility to autoimmune diseases and drug hypersensitivity, e.g., HLA-B*57:01 and abacavir hypersensitivity. HLA restriction also dictates peptide selection for cancer and infectious disease vaccines.
Antigen presentation
The process whereby peptide fragments derived from intracellular or engulfed proteins are bound to MHC molecules and displayed to T cells. In the class I pathway, proteasomal degradation is followed by TAP-mediated transport into the ER, whereas in the class II pathway, exogenous antigens are degraded in endosomes before binding. Recognition of the peptide–MHC complex by T-cell receptors determines the direction of the immune response. Tumor cells often evade immune surveillance by disrupting this pathway or down-regulating MHC expression. Vaccine development relies on selecting epitopes that are efficiently presented.
Allograft rejection
The phenomenon in which the recipient’s immune system attacks donor tissues transplanted between genetically non-identical members of the same species. Acute rejection is mainly driven by T cells directly recognizing MHC disparities, while chronic rejection involves antibodies and inflammation that damage graft vasculature. Clinically, HLA matching combined with immunosuppressive drugs mitigates the problem. Current research seeks immune tolerance via regulatory T cells and co-stimulation blockade. In xenotransplantation using genome-edited pigs, altering MHC-like molecules is also a critical challenge.
Tissue typing
A pre-transplant test that compares donor and recipient HLA types to assess compatibility. Historically based on micro-cytotoxicity assays, it now employs PCR-SSP and next-generation sequencing for high-resolution typing. Cross-match tests detect donor-specific antibodies; a positive result signals higher rejection risk. Better matches allow lower doses of immunosuppressants, reducing side effects. In hematopoietic stem cell transplantation, precise HLA matching is indispensable because it directly affects engraftment and graft-versus-host disease incidence.
Genetic polymorphism
The presence of multiple alleles at a given locus, leading to sequence variation among individuals. The MHC region is among the most polymorphic in the human genome, with mutations concentrated in peptide-binding domains. Polymorphism is thought to be maintained by evolutionary forces such as pathogen adaptation and mate choice. Specific alleles, however, confer risks for autoimmunity or drug adverse reactions. In large-scale genomics, the structural complexity of MHC polymorphism poses challenges for accurate sequencing and assembly.
T cell receptor
A heterodimeric membrane protein on T cells that recognizes peptide–MHC complexes. The α and β (or γδ) chains diversify through V(D)J recombination, generating millions of specificities. The receptor reads both peptide side chains and MHC residues, establishing MHC restriction. The affinity and dwell time of TCR–MHC interactions influence the strength of the immune response and T-cell fate decisions. In cancer immunotherapy, TCR engineering introduces high-affinity receptors to create tumor-specific T cells.