VARIABILITY ANALYSIS OF THE T-CELL RECEPTORS USING 3 VARIABILITY INDEXES

In the absence of a three-dimensional structure for TCR molecules, sev eral attempts to identify their hypervariable regions by variability m ethods have been made; this subject is still troublesome. In this pape r three different variability indexes were used: (i) the Kabat index, which is the classical measure of sequence variability, (ii)the modifi ed Kabat index, successfully used in the beta-chain of T-cell receptor s and (iii) an information-theoretical entropy concept, recently propo sed as an improved measure of the variability. In order to identify th e hypervariable regions in the TCR sequences, a Fourier filtering was applied on each variability profile. Results show that the three varia bility indexes have distinct resolutions for different levels of varia bility. Thus, the simultaneous use of these indexes compensates for th e deficiency of any one of them in estimating variability. Applying th e Fourier filtering, it is found that the hypervariable regions here i dentified, roughly coincide with the defined CDR-2 and CDR-3 in TCR by analogy with Ig. However, no hypervariable in the CDR-1 of alpha- and beta-chains was found. The study on the influence of sample size in v ariability analysis, indicates that results are independent of the sam ple size. Considering current structural models of TCR-peptide-MHC int eraction, one can suggest that the low-variability characteristics of these regions is inherently related to the interaction with relatively conserved region on the alpha-helices of MHC. (C) Munksgaard 1995.