Oligoclonality in the human CD8+ T cell repertoire in normal subjects and monozygotic twins: implications for studies of infectious and autoimmune diseases

Mol Med. 1995 Sep;1(6):614-24.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Twin Study

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Base Sequence
  • CD8-Positive T-Lymphocytes / immunology*
  • Communicable Diseases / genetics
  • Communicable Diseases / immunology*
  • DNA Primers
  • DNA, Complementary
  • Humans
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction / methods
  • Receptor-CD3 Complex, Antigen, T-Cell / genetics*
  • Reference Values
  • Twins, Monozygotic / genetics*


  • DNA Primers
  • DNA, Complementary
  • Receptor-CD3 Complex, Antigen, T-Cell