antibody repertoire dominated by few clones

#Antibody repertoire dominated by few clones plus#

Therefore, we set out to define the respective sizes of the adaptive and innate T cell populations associated with CD1d, the only CD1 isotype expressed in mice, and the one shared by most, though perhaps not all 24, mammals thus far examined. The coexistence of innate and adaptive TCR recognition would be a unique and fascinating aspect of the CD1 system, likely to have important evolutionary implications for the protective value of lipid, as opposed to peptide, recognition.

#Antibody repertoire dominated by few clones plus#

These prominent Vα14 and Vδ1 CD1-restricted subsets seem to obey a logic that differs markedly from adaptive lymphocytes but closely resembles other “innate” lymphocytes, such as B-1 B cells, γδ T cells, and NK cells, which express invariant or semiinvariant antigen receptors and survey self-antigens or promiscuous (self plus foreign) antigens that are induced or exposed in conditions of infection, stress, or transformation 11, 12, 13, 14, 15. Vδ1 γδ T cells constitute a major population of human intraepithelial intestinal lymphocytes and are considered to be part of the innate rather than adaptive immune system 10. Despite their limited TCR repertoire, Vα14 NKT cells constitute a disproportionate fraction of the mature T cell population of the adult spleen (2%), thymus (10%), bone marrow (20%), and liver (30%). They also express several receptors associated with the NK lineage. Vα14 NKT cells express a TCR repertoire made of an invariant Vα14-Jα18 chain (Vα24-Jα18 in humans) mainly associated with the variable Vβ8 chains (Vβ11 in humans reference 9) and uniformly recognize the glycolipid α-galactosylceramide (αGalCer) at picomolar concentrations 4. They also include prominent T cell subsets expressing characteristics of innate rather than adaptive antigen recognition such as the CD1d autoreactive Vα14 NKT cells and the CD1c autoreactive Vδ1 T cells. For example, they include an inordinate proportion of double negative (DN) CD4 −CD8 − αβ T cells 3, 5, a phenotype also associated with some unusual autoreactive, MHC-restricted T cells 6, 7, 8. Altogether, these findings imply that lipid recognition by CD1d-restricted T cells may have largely evolved as an innate rather than an adaptive arm of the mouse immune system.ĬD1-restricted T cells differ in several interesting ways from MHC-restricted T cells. Finally, we demonstrate that the MHC-restricted TCR repertoire is essentially non–cross-reactive to CD1d. They more closely resemble other lineages of innate lymphocytes such as B-1 B cells, γδ T cells, and NK cells, which express invariant or semiinvariant autoreactive receptors. Thus, CD1d-restricted T cells differ profoundly from MHC-peptide–specific T cells by their predominant use of autoreactive and semiinvariant, rather than naive and diverse, TCRs. Furthermore, zooming in on the CD1d-dependent non-Vα14 T cells, we found that, like Vα14 NK T cells, they mainly expressed recurrent, CD1d autoreactive TCR families and had a natural memory phenotype.

Surprisingly, up to 80% of the CD1d-dependent T cells were stained by tetramers of CD1d/α-galactosylceramide, which specifically identify the previously described CD1d autoreactive Vα14-Jα18/Vβ8 natural killer (NK) T cells. To define the phenotype and T cell receptor (TCR) repertoire of CD1d-dependent T cells, we compared the populations of T cells that persisted in major histocompatibility complex (MHC)-deficient mice, which lack mainstream T cells, with those from MHC/CD1d doubly deficient mice, which lack both mainstream and CD1d-dependent T cells.