Human extracellular proteins display a different pattern of local sequence similarity with the four classes of human T-cell receptor V regions than foreign proteins and human intracellular proteins: a preliminary report

Abstract

A pool of 110 randomly selected/generated amino acids sequences was used to perform specific local sequence similarity alignment analysis with the pool of 279 reported sequences of human T-cell receptor (TCR) V-regions. The 110 analyzed sequences were divided, according to their origin and nature, into six protein groups, as: human intracellular (hi), extracellular/transmembrane (he) and extracellular adhesive matrix (ha) proteins, average human proteins (hum), proteins of non-human origin (nhum) and randomly generated quasi-protein sequences (r). These sequences were decomposed into all their overlapping 11-mer segments, generating a total of 56 836 derived peptides (at least 8000 per group). Each derived peptide was aligned with the 279 human TCR V-regions and assigned to the category (alpha-like, beta-like, gamma-like or delta-like) corresponding to the class (V alpha, V beta, V gamma or V delta) of the V-region encompassing the most similar segment, as determined by the performed similarity-search. The six protein groups were found to differ significantly in their distribution of derived peptides among the four categories. According to the binomial tests results, human proteins from the extracellular compartment (he, ha) comprise a higher proportion of delta-like segments (P = 2.3 x 10(-2) and P LT 10(-8), respectively) than the average human proteins (hum). In addition, and in accordance with this finding, proteins that are normally not found in that topological compartment comprise a lower proportion of delta-like peptides (P = 1.4 x 10(-5) and P LT 10(-8) for groups nhum and hi, respectively) than the average human proteins (hum). In contrast, these proteins comprise a higher proportion of gamma-like segments (P = 8.3 x 10(-3), P = 1.4 x 10(-3) and P = 1.7 x 10(-4), for groups r, nhum and hi, respectively) than the average human proteins (hum). These findings indicate significant differences between proteins encountered in the extracellular compartment-that are normally immunologically tolerated-and those the presence of which is usually non-tolerated. The results suggest that the discrimination and the reaction of the human immune network to proteins found in the extracellular compartment correlate with the proteins pattern of preferential local sequence similarity with the V gamma and V delta classes of human TCR V-regions, implying a specific and an important role of gamma delta-cells in the maintenance of the immune homeostasis. Whether this implication represents a rule associated with self-tolerance, will be investigated by future analyses. (C) 1998 Elsevier Science B.V. All rights reserved.