[The HLA system in rheumatic practice: from structure to typing]

The HLA system regulates specific immune responses by presenting a processed foreign antigen (likely a peptide) to T lymphocytes. The peptide is associated with an HLA class I molecule (HLA A, B, C) when CD8 + T lymphocytes are activated to become cytotoxic. Alternatively when a peptide is associated with an HLA class II (HLA DR, DQ, DP) molecule CD4 + T cells are activated (helper T cells) which in turn stimulate B cells to produce specific antibodies. Recent studies have unravelled the three-dimensional structure of one HLA class I molecule and provided a framework for the 3D structure of class II molecules. This allow an understanding of the complex structure-function relationship of the HLA molecule with the antigen and the T cell receptors. Apart from transplantation the importance of the HLA system in medicine is due to its central role in auto-immunity. The HLA system is involved both at the genetic level (various disease susceptibilities are associated with particular alleles of HLA class I or class II) and at the phenotypic level (hyperexpression of HLA class I molecules and aberrant expression of class II molecules are observed on diseased tissues). Recently several molecular techniques have been developed for HLA typing including isoelectrofocalisation (IEF), two dimensional gel electrophoresis (2D PAGE) RFLP or oligonucleotide probing (ASO). They provide an accurate and precise way of typing and thus are very valuable in studying HLA and disease associations by defining the molecules and epitopes responsible for high genetic susceptibility or resistance to the relevant disease.