CHARACTERIZATION OF THE PRIMARY STRUCTURE OF T-CELL RECEPTOR-BETA CHAINS IN CELLS INFILTRATING THE SALIVARY-GLAND IN THE SICCA SYNDROME OF HIV-1 INFECTION - EVIDENCE OF ANTIGEN-DRIVEN CLONAL SELECTION SUGGESTED BY RESTRICTED COMBINATIONS OF V-BETA J-BETA GENE SEGMENT USAGE AND SHARED SOMATICALLY ENCODED AMINO-ACID-RESIDUES

Infection with HIV-1 occasionally results in a sicca syndrome. termed the diffuse infiltrative lymphocytosis syndrome, characterized by infiltration of the salivary glands with a predominance of CD8 T cells. This response is strongly associated with certain MHC class I and class II alleles. To define the salivary gland T cell receptor (TCR) repertoire, the primary structure of the TCR beta-chains was determined using in situ cDNA synthesis followed by the ''anchored'' polymerase chain reaction. The sequences of 59 beta-chains from five individuals with diffuse infiltrative lymphocytosis syndrome shared structural features suggesting antigenic clonal selection. Certain combinations of Vbeta Jbeta gene segments were selectively overrepresented in the repertoire sample, demonstrating a common restricted usage of certain Vbeta and Jbeta gene segments. The beta-chains derived from these overrepresented Vbeta Jbeta combinations revealed a preference for specific amino acids at position 97 in the third complementarity-determining region, a residue postulated to contact peptide antigen. Moreover, the nucleotides encoding this position were not germline in origin. TCR beta-chains in nonoverrepresented Vbeta Jbeta combinations did not exhibit preferential usage of selected somatically encoded residues. The pattern of TCR beta-chains expressed in the salivary gland of a control person with primary Sjogren's syndrome was considerably more heterogeneous and different from that found in diffuse infiltrative lymphocytosis syndrome.