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 infi ltration of the salivary glands with a predominance of CD8 T cells. Th is response is strongly associated with certain MHC class I and class II alleles. To define the salivary gland T cell receptor (TCR) reperto ire, 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 d iffuse infiltrative lymphocytosis syndrome shared structural features suggesting antigenic clonal selection. Certain combinations of Vbeta J beta gene segments were selectively overrepresented in the repertoire sample, demonstrating a common restricted usage of certain Vbeta and J beta gene segments. The beta-chains derived from these overrepresented Vbeta Jbeta combinations revealed a preference for specific amino aci ds at position 97 in the third complementarity-determining region, a r esidue postulated to contact peptide antigen. Moreover, the nucleotide s encoding this position were not germline in origin. TCR beta-chains in nonoverrepresented Vbeta Jbeta combinations did not exhibit prefere ntial usage of selected somatically encoded residues. The pattern of T CR beta-chains expressed in the salivary gland of a control person wit h primary Sjogren's syndrome was considerably more heterogeneous and d ifferent from that found in diffuse infiltrative lymphocytosis syndrom e.