Major histocompatibility complex proteins structure

Major histocompatibility complex (MHC) proteins are essential components of the immune system (1). One speeific role is for them to bind and present cellularly derived peptides (-8-10 amino acids - MHC Class I peptides) at the cell surface. These peptides are subsequently challenged by cytolytic T-lymphocytes (CTL s) which are programmed to differentiate between self and exogenous peptides. T-cell recognition of these latter peptides initiates a response that ultimately results in cell lysis and death of the infected cell. Hence, structural characterization of such peptides could potentially result in the development of therapeutie treatments of a number of infectious disease states such as viral cancers, AIDS, and autoimmune disease. However, the task of sequencing such peptides is difficult since MHC class I proteins can bind and present 10,000-15,000 different cellularly derived peptides present at the sub-pieo-femtomole level (2,3). 

Superantigen target three key proteins of the adaptive immune response, namely the T cell receptor (TCR), the B cell receptor (BCR) and major histocompatibility complex class II (MHC II) proteins. All are members of the Ig superfamily, and contain domains of similar tertiary structures, although MHC II contains two non-Ig-like domains. The structure of the Ig-like domain consists of two (3-sheets, each of which comprises a series of anti-parallel (3-strands, connected by loops of varying length. Ig domain structures embody two separate functions the first is the association with antigens, with each other and with other proteins, such as Fc receptors or complement, while the second is maintenance of the structural integrity of the domain itself. 

The most familiar of the recognition proteins are antibodies or immunoglobulins. Another class of recognition molecules consists of the proteins called T-cell receptors but less is known of their properties and structure. A third class of proteins with a vital role in immune recognition is those in the major histocompatibility complex (MHC). The MHC proteins were discovered in tissue-grafting experiments. The structure of the major histocompatibility antigen has been determined by Bjorkman et al (1987). 

Lck, a 56-kDa protein, has originally been characterized as a Src-related tyrosine kinase that is specifically expressed in lymphocytes (Lck is named after lymphocyte kinase). In T-cells, Lck associates with CD4/CD8 cell surface receptor for major histocompatibility complex and, upon interaction with antigen-presenting cells, it will be activated by dephosphorylation in the carboxyl-terminal tyrosine residue, as catalyzed by CD45 phosphatase. In murine eggs, it has been reported that CD4-hke structures on the vitelline membranes are involved in gamete interaction, and that Lck-hke protein could have been detected in association with those CD4-like structures (Mori et al. 2000 Mori et al. 1991). While these studies have been done with the use of sjjedfic monoclonal antibodies (e.g. immunofluorescent and immunochemical approaches), biochemical and molecular biological identifications have not yet been demonstrated. 

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