Major histocompatability complex structure

Ironically, SE or TSST-1 concentrations that cause T-cell proliferation do not always correlate with receptor affinity. For instance, SEE binds HLA-DR with 100-fold lower affinity relative to the very similarly structured SEA however, SEE stimulates T-cell proliferation to equivalent levels as SEA. The dose-response curves for cytokine and chemokine production in vitro by staphylococcal superantigen-stimulated cells are also very similar despite differences in affmity/specificity for major histocompatibility complex class II and T-cell receptor V/3 molecules. Overall, these observations suggest that the biological effects of staphylococcal superantigens are induced at rather low, nonsaturating occupancy rates not readily classified by typical biokinetics. 

Bjorkman, P. J., and Parham, P. (1999). Structure, function and diversity of class I major histocompatibility complex molecules. Ann. Rev. Biochem. 90, 253-288. 

Borrego, F., Rabat, J., Kim, D.-K., Lieto, L., Maasho, K., and Pena, J. et al. (2002). Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells. Mol. Immunol. 1063, 1-24. 

Willcox, B. E., Thomas, L. M., and Bjorkman, P.J. (2003). Crystal structure of HLA-A2 bound to LIR-1, a host and viral major histocompatibility complex receptor. Nat. 

P.J. Bjorkman and P. Parham. 1990. Structure, function, and diversity of class 1 major histocompatibility complex molecules Rev. Biochem. 59 253-288. (PubMed)... 

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). 

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