Frequency analysis of amino acids in the recognition regions of T-cell receptors

• Published in: BioSystems 1996, Vol.39 (1), p.77-86
• Main Authors: Lara-Ochoa, F., Almagro, J.C., Vargas-Madrazo, E., Mendez, I.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Binding Sites - genetics; Biometry; Evolution, Molecular; Fractals; Humans; Immunoglobulin Variable Region - genetics; Long-range interactions; Models, Biological; Molecular Structure; Pattern recognition; Receptors, Antigen, T-Cell - chemistry; Receptors, Antigen, T-Cell - genetics; T-cell receptors; Zipf Law
• ISSN: 0303-2647; 1872-8324
• DOI: 10.1016/0303-2647(95)01602-3

In immunoglobulins (Igs), key amino acids in the Complementarity Determining Regions (CDR) are responsible for maintaining specific conformations called canonical structures. In T-cell receptors (TCRs), protein members of the Ig superfamily, the corresponding residues for maintaining these canonical structures have not been found. In previous studies we have found in Igs that the frequency of use of amino acids in some positions of the CDRs follows an inverse power law distribution, while the frequency of amino acids in the rest of the positions of the CDRs follows an exponential law distribution. The positions that follow the inverse power law distribution are precisely those involved in maintaining the canonical structures, while those positions for which the distribution fits the exponential distribution are those that should be properly involved in the recognition mechanism. In this paper, when the same analysis is applied to the use frequency of amino acids on the CDRs of TCRs, it is found that some positions that have been previously identified as having a structural role are those fitting the inverse power law. That finding combined with the cooperative or long-range interaction properties of systems that follow the inverse power law leads us to propose that the lack of determined key residues in certain positions is compensated by ‘equivalent’ residues in other positions within the CDRs in order to maintain the canonical structures. Other positions that follow the exponential distribution are those which can be involved in the recognition process. These results coincide with a computer-generated model of TCR/peptide/MHC interaction previously published by the authors.