IAVI Report - July / September 2001

The Human Leukocyte Antigen (HLA) system is, in some respects, the immunological equivalent of a sophisticated alarm system. HLA molecules are produced within human cells, and act as receptacles for fragments of cellular or foreign (e.g., viral) proteins. The HLA molecules then display these fragments (known as peptides) on the outside of the cell; a single cell is typically adorned with several hundred thousand different HLA-peptide complexes. This process allows circulating T-cells to survey the HLA-peptide complexes for signs of any foreign peptides that might indicate the presence of a pathogen.

HLA molecules are divided into two major classes (I and II), which are recognized by different subsets of T-cells. The CD8 molecule on CD8+ T-cells interacts with class I HLA molecules. Likewise, the CD4 molecule on CD4+ T-helper cells interacts class II molecules. In both cases, the peptide associated with the HLA molecule is recognized by a structure on the T-cell called a T-cell receptor (TCR).

The critical aspect of the HLA system for immunity is that both class I and II molecules come in hundreds of different versions, dependent on the HLA genes inherited from our parents. The precise shape and size of an HLA molecule governs its ability to associate with a diverse array of peptides and present them to T-cells. HLA molecules thus exert a profound influence on the body's ability to mount a broad and effective T-cell response to any given pathogen.

Each individual has over 40 different genes that encode HLA molecules. The class I genes are divided into different regions (or loci), with the most important being HLA-A, -B and -C. The major class II genes are HLA-DP, -DQ and -DR. There are many variations of these genes in the human population and thus many variant HLA molecules. The different versions of the genes are known as alleles, and a complex classification system is used to characterize the specific HLA alleles that an individual has inherited The known alleles are numbered, for example, as in HLA-A2 or HLA-DR5. Analysis of the HEPS women has identified several class I and II alleles associated with resistance (see main article "Closing in on Immune Protection in the Women of Pumwani").

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©2001. The IAVI Report.

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