The Journal of Immunology, Vol 138, Issue 1 204-212, Copyright © 1987 by American Association of Immunologists

ARTICLES

Strong conformational propensities enhance T cell antigenicity

JL Spouge, HR Guy, JL Cornette, H Margalit, K Cease, JA Berzofsky and C DeLisi

The ability to predict T cell antigenic peptides would have important implications for the development of artificial vaccines. As a first step towards prediction, this report uses a new statistical technique to discover and evaluate peptide properties correlating with T cell antigenicity. This technique employs Monte Carlo computer experiments and is applicable to many problems involving protein or DNA. The technique is used to evaluate the contribution of various peptide properties to helper T cell antigenicity. The properties investigated include amphipathicities (alpha and beta), conformational propensities (alpha, beta, turn and coil), and the correlates of alpha-helices, such as the absence of helix-breakers and the positioning of the residues which stabilize alpha-helical dipoles. We also investigate segmental amphipathicity. (A peptide has this property when it contains at least two disjoint subpeptides, one hydrophobic, one hydrophilic.) Statistical correlations and stratifications assessed independent contributions to T cell antigenicity. The findings presented here have important implications for the manufacture of peptide vaccines. These implications are as follows: if possible, peptide vaccines should probably be those protein segments which have a propensity to form amphipathic alpha-helices, which do not have regions with a propensity to coil conformations, and which have a lysine at their COOH-terminus. The last two observations are of particular use in manufacturing peptides vaccines: they indicate where the synthetic peptides should be terminated. These implications are supported by the findings given below. The significances (p values) support the following statistical generalites about antigenic conformations: most helper T cell antigenic sites are amphipathic alpha-helices; alpha-helical amphipathicity and propensity to an alpha-helical conformation contribute independently to T cell antigenicity; there is evidence that some T cell antigenic sites are beta conformations instead of alpha-helices; T cell antigenic sites avoid random coiled conformations; and T cell antigenic sites are usually not segmentally amphipathic. alpha-Helical amphipathicity was significant, but segmental amphipathicity was not. This has implications for the dimensions of the structure interacting with the hydrophobic portion of an amphipathic T cell antigenic site. Lysines are unusually frequent at the COOH-terminal of T cell antigenic sites, even after accounting for tryptic digests. These lysines can stabilize alpha-helical peptides by a favorable interaction with alpha-helical dipoles.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				D. G. McNeel, L. D. Nguyen, and M. L. Disis Identification of T Helper Epitopes from Prostatic Acid Phosphatase Cancer Res., July 1, 2001; 61(13): 5161 - 5167. [Abstract] [Full Text] [PDF]

				H.M. Grey, S. Demotz, S. Buus, and A. Sette Studies on the Nature of Physiologically Processed Antigen and on the Conformation of Peptides Required for Interaction with MHC Cold Spring Harb Symp Quant Biol, January 1, 1989; 54(0): 393 - 399. [Abstract] [PDF]

				E. Unanue and P. Allen The basis for the immunoregulatory role of macrophages and other accessory cells Science, May 1, 1987; 236(4801): 551 - 557. [Abstract] [PDF]

				M. Good, W. Maloy, M. Lunde, H Margalit, J. Cornette, G. Smith, B Moss, L. Miller, and J. Berzofsky Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein Science, February 27, 1987; 235(4792): 1059 - 1062. [Abstract] [PDF]