Editorial

A complete understanding of the biochemical and come from studying the details of the x-ray struc-tures of MHC molecules complexed with peptides.immunological mechanisms that underlie recogni-

tion of antigens by T cells is the rosetta stone for P. Jensen has masterfully reviewed the class II pro-cessing and presentation pathway. A peptide chem-future vaccine design and control of autoimmunity.

Peptides are the target of immune recognition by T ist will see immediately that there are numerousimmunologically relevant opportunities for design-cells, and these peptides bind to peptide receptors,

so-called major histocompatibility (MHC) mole- ing and synthesizing peptide mimics to alter im-mune processing and thereby to alter the repertoirecules. There are two types of MHC molecules. Class

I MHC bind peptides presented to cytotoxic T cells, of peptides available presentation and subsequentimmune recognition. E. Fowler and H. L. Weinerwhile class II MHC molecules bind peptides pre-

sented to helper T cells. In each case these peptides have detailed the mechanisms underlying oral toler-ance, the phenomenon of systemic, antigen-specific,are the product of enzymatic degradative pathways

operating in the cytosol or in endosomal compart- immunological hyporesponsiveness, which resultsfrom the oral administration of a protein. Orallyments, respectively. In this issue of Peptide Science,

four areas of immune processing and processing are administered autoantigens have been shown to sup-press a wide variety of autoimmune diseases, andpresented. M. Bogyo, M. Gaczynska, and Hidde

Ploegh describe the degradation of protein antigens the relevance of these studies to the design of immu-nosuppressives and vaccines cannot be overesti-by proteosomes, multisubunit complexes responsi-

ble for the degradation of cytosolic proteins, prior mated. There is little doubt that peptide chemistswill play an important part in unraveling the nu-to complexing of the liberated peptides to class I

major histocompatibility complex antigens and the ances of these biochemical / immunological path-ways.effects of proteosome inhibitors. These studies will

be of great interested to peptide chemists capable These four reviews are a primer for chemistsinterested in applying their knowledge to therapeu-of designing and synthesizing novel inhibitors that

may selectively regulate protein antigen processing tic regulation of immunity. The potential for novelpeptide-based vaccines and processing/presentationand thereby alter the immune response to foreign

or autoimmune antigens. M. A. Batalia and E. J. inhibitors to revolutionize the treatment of autoim-mune diseases (e.g., type 1 diabetes mellitus andCollins have described in exquisite detail the molec-

ular details about how peptides bind to class I and rheumatoid arthritis) and cancer is clear.II MHC molecules. For peptide chemists interestedin designing and synthesizing peptides as immuno-

JOHN A. SMITHgens or inhibitors of immune recognition, this re-view offers a glimpse of the revelations that have Issue Editor

Biopolymers (Peptide Science), Vol. 43, 267 (1997)q 1997 John Wiley & Sons, Inc. CCC 0006-3525/97/040267-01

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