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MHC molecules, also known in the human as human leukocyte antigens (HLA), display peptides on antigen presenting cell surfaces for subsequent T cell recognition. Identification of these antigenic peptides is especially important for developing peptide-based vaccines. Consequently experimental and computational approaches have been developed for their identification. A major impediment to such an approach is the extreme polymorphism of HLA, which is in fact the basis for differential peptide binding. This problem can be mitigated by the observation that despite such polymorphisms, HLA molecules bind overlapping set of peptides, and therefore, may be grouped accordingly into supertypes. Here we describe a method of grouping HLA alleles into supertypes based on analysis and subsequent clustering of their peptide binding repertoires. Combining this method with the known allele and haplotype gene frequencies of HLA I molecules for five major American ethnic groups (Black, Caucasian, Hispanic, Native American, and Asian), it is now feasible to identify supertypic combinations for prediction of antigenic peptide, offering the potential to generate peptide-vaccines with a population coverage ≥ 95%, regardless of ethnicity. One combination including five distinct supertypes is available online at our PEPVAC web server (http://immunax.dfci.harvard.edu/PEPVAC/). Promiscuous peptides predicted to bind to these five supertypes represent around 5% of all possible peptide binders from a given genome.

Monocytes and macrophages play an important role in the immune system through their cytotoxic activity, production of mediators and cytokines, ability to phagocytose native and opsonised antigens and pre-sentation of antigenic peptides to T cells. These functions of monocytes/ macrophages are influenced by the action of several cytokines: IFN-γ, GM-CSF, M-CSF and TNF-α activate monocytes, whereas IL-4, IL-13, TGFβ and IL-10 are potent monocyte deactivators. IL-10 plays a major role as dampener of immune responses through its deactivating potential of monocyte/macrophage functions.1,2,3 The activities of IL-10 on mono-cyte functions are the subject of this chapter.

Activation of class II-restricted T cells requires the formation of a trimolecular complex between antigenic peptide fragments, class II MHC molecules, and the T cell receptor (Buus et al. 1987). In contrast to the substantial body of evidence characterizing the interaction between synthetic peptides and class II molecules, essentially no data are available on the nature of the antigen resulting from in vivo processing of protein molecules. It has been postulated that fragments arise from limited proteolytic degradation of native antigens inside acidic compartments of the antigen-presenting cells; however, up to now no direct chemical characterization of physiologically processed peptides has been presented. In this paper we review experiments that we have performed that provide the first partial characterization of a physiologically processed antigen.