Cellular typing and functional heterogeneity of MHC-encoded products

Abstract

Definition of many HLA-encoded products is possible by cellular techniques, whereby T cells can act as highly discriminatory reagents in lympho-proliferative or cytotoxicity assays. Homozygous typing cells can be used in primary mixed lymphocyte cultures to identify HLA-Dw specificities and lymphocytes primed to recognise a range of class II determinants can be used in secondary cultures. Such reagents have been raised to specifically identify the DP allelic series. Studies using cytotoxic T lymphocytes are now providing evidence for the further resolution of HLA specificities into their subtypes. Clonal expansion of cellular cultures and the introduction of T cell cloning techniques are leading to the production of highly specific reagents. The functional heterogeneity of HLA class II determinants and their influence on cellular typing assignments are considered in detail. Anomalous typing reactions are discussed in relation to the action of suppressor activating determinants together with the possible modulation of responses by DQ determinants. The contribution of class II products towards Dw assignments is critically assessed and evidence is provided to support the view that Dw is a distinct entity from both DQ and DR. The relationship of Dw to DR and DQ is examined in the light of immunochemical and molecular biological studies.