       Document 0434
 DOCN  M9640434
 TI    Oligoclonality in the human CD8+ T cell repertoire in normal subjects
       and monozygotic twins: implications for studies of infectious and
       autoimmune diseases.
 DT    9604
 AU    Monteiro J; Hingorani R; Choi IH; Silver J; Pergolizzi R; Gregersen PK;
       Department of Medicine, North Shore University Hospital/Cornell;
       University Medical Center, Manhasset, New York, USA.
 SO    Mol Med. 1995 Sep;1(6):614-24. Unique Identifier : AIDSLINE MED/96091385
 AB    BACKGROUND: We have previously demonstrated CD8+ T cell clonal dominance
       using a PCR assay for the CDR3 length of T cell receptors belonging to a
       limited number of TCRBV segments/families. In this study, we have
       modified this approach in order to analyze more comprehensively the
       frequency of oligoclonality in the CD8+ T cell subset in 25 known TCRBV
       segments/families. In order to assess the relative roles of genes and
       environment in the shaping of a clonally restricted CD8+ T cell
       repertoire, we have analyzed clonal dominance in the CD8+ T cell
       population of monozygotic twins, related siblings, and adoptees.
       MATERIALS AND METHODS: Oligoclonality was assessed in the CD8+ T cell
       subsets using a multiplex PCR approach to assay for CDR3 length
       variation across 25 different TCRBV segments/families. Specific criteria
       for oligoclonality were established, and confirmed by direct sequence
       analysis 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
       monozygotic (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
       dominant CD8+ T cell clones that were highly similar in sequence in both
       members of some twin pairs. Not a single example of such similarity was
       observed in normal controls or siblings. CONCLUSIONS: Oligoclonality of
       circulating CD8+ T cells is a characteristic feature of the human 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 to
       evaluate CD8+ T cell oligoclonality in the setting of infection or
       autoimmune disease. Further phenotypic and functional characterization
       of these clonally expanded T cells should provide insight into normal
       immune homeostasis.
 DE    Adolescence  Adult  Amino Acid Sequence  Autoimmune
       Diseases/GENETICS/*IMMUNOLOGY  Base Sequence  Communicable
       Diseases/GENETICS/*IMMUNOLOGY  Comparative Study  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  DNA Primers  DNA, Complementary  Human
       Middle Age  Molecular Sequence Data  Polymerase Chain Reaction/METHODS
       Receptor-CD3 Complex, Antigen, T-Cell/*GENETICS  Reference Values
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Twins,
       Monozygotic/*GENETICS  JOURNAL ARTICLE  TWIN STUDY

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

