Characterization of the primary structure of T cell receptor β 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 Vβ Jβ 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 β-chains was determined using in situ cDNA synthesis followed by the "anchored" polymerase chain reaction. The sequences of 59 β-chains from five individuals with diffuse infiltrative lymphocytosis syndrome shared structural features suggesting antigenic clonal selection. Certain combinations of Vβ Jβ gene segments were selectively overrepresented in the repertoire sample, demonstrating a common restricted usage of certain Vβ and Jβ gene segments. The β-chains derived from these overrepresented Vβ Jβ 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 β-chains in nonoverrepresented Vβ Jβ combinations did not exhibit preferential usage of selected somatically encoded residues. The pattern of TCR β-chains expressed in the salivary gland of a control person with primary Sjögren's syndrome was considerably more heterogeneous and different from that found in diffuse infiltrative lymphocytosis syndrome.