OLIGOCLONALITY IN THE HUMAN CD8(-CELL REPERTOIRE IN NORMAL SUBJECTS AND MONOZYGOTIC TWINS - IMPLICATIONS FOR STUDIES OF INFECTIOUS AND AUTOIMMUNE-DISEASES() T)

Background: We have previously demonstrated CD8(+) T cell clonal domin ance using a PCR assay for the CDR3 length of T cell receptors belongi ng to a limited number of TCRBV segments/families. in this study, we h ave modified this approach in order to analyze more comprehensively th e frequency of oligoclonality in the CD8(+) T cell subset in 25 known TCRBV segments/families. In order to assess the relative roles of gene s and environment in the shaping of a clonally restricted CD8(+) T cel l repertoire, we have analyzed clonal dominance in the CD8(+) T cell p opulation of monozygotic twins, related siblings, and adoptees. Materi als and Methods: Oligoclonality was assessed in the CD8(+) T cell subs ets using a multiplex PCR approach to assay for CDR3 length variation across 25 different TCRBV segments/families. Specific criteria for oli goclonality were established, and confirmed by direct sequence analysi s of the PCR products. This assay was used to investigate the CD8(+) T cell repertoire of 56 normal subjects, as well as six sets of monozyg otic (MZ) twins. Results: Seventy-two percent of normal subjects (n = 56) had evidence of oligoclonality in the CD8(+) T cell subset, using well-defined criteria. Although MZ twins frequently displayed CD8(+) T cell clonal dominance, the overall pattern of oligoclonality was very diverse within each twin pair. However, we occasionally observed domi nant CD8(+) T cell clones that were highly similar ip sequence in both members of some twin pairs. Not a single example of such similarity w as observed in normal controls or siblings. Conclusions: Oligoclonalit y of circulating CD8(+) T cells is a characteristic feature of the hum an immune system; both host genetic factors and environment shape the pattern of oligoclonality in this T cell subset. The high frequency of this phenomenon in normal subjects provides a background with which t o evaluate CD8(+) T cell oligoclonality in the setting of infection or autoimmune disease. Further phenotypic and functional characterizatio n of these clonally expanded T cells should provide insight into norma l immune homeostasis.