Analysis of the TCRBV repertoire of T cells in normal, human skin: evidence for a restricted diversity.

Alpha beta T cells constitute an important component in the first line of immunologic defense in human skin. In order to determine the local selection forces driving T cell diversity, we studied the T cell receptor repertoire in normal human skin and compared it with that of matched blood samples. Using semiquantitative reverse transcription-polymerase chain reaction the expression of T cell receptor beta-chain V genes was determined. The majority of skin, but not blood T cells, revealed a bias towards usage of T cell receptor beta-chain V2 and V6. Whereas sequencing of T cell receptor beta-chain V2 and V6 polymerase chain reaction products showed a heterogeneous clonal distribution within these beta-chain V gene families, the analysis of other selected either over- or underrepresented beta-chain V gene families (BV3, BV12, BV13S1, BV17) revealed numerous identical T cell receptor beta-chain V transcript sequences that were not detected in blood. Restricted T cell receptor diversity in terms of beta-chain V gene preferences or clonal expansion was observed in skin samples of donors from all ages (0.5-87 y). Hence, the repertoire of T cells in normal human skin is apparently subjected to skin-specific selection throughout life. According to our data, this process could involve superantigens, which favor polyclonal accumulation of T cells using certain beta-chain V genes, as well as antigens, which induce clonal T cell expansion. Our results furthermore indicate, that T cell receptor beta-chain V repertoire restrictions do not necessarily result from disease-associated activation of the skin immune system, but could reflect regular mechanisms of immunologic homeostasis within the epithelial surface of the body.