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Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
Published on: March 14, 2011
Killer cells reactive to altered-self antigens can also be alloreactive
Summary
Cytotoxic T lymphocytes recognize "altered-self" targets, like foreign minor antigens plus self H-2 antigens. This study found that these cells can also lyse allogeneic targets, suggesting cross-reactivity between self and non-self recognition.
Area of Science:
- Immunology
- Cellular immunology
- T cell biology
Background:
- Cytotoxic T lymphocytes (CTLs) play a crucial role in adaptive immunity.
- CTLs can recognize foreign antigens presented by self-major histocompatibility complex (MHC) molecules, termed "altered-self" recognition.
- Alloreactive CTLs recognize foreign MHC molecules on allogeneic cells.
Purpose of the Study:
- To investigate the specificity and cross-reactivity of cytotoxic T lymphocytes (CTLs) generated against minor histocompatibility differences.
- To determine if CTLs recognizing "altered-self" antigens can also recognize allogeneic targets.
- To explore the potential for shared receptors in recognizing self-plus-foreign antigens and foreign-foreign antigens.
Main Methods:
- Immunization of mice against minor histocompatibility differences in vivo and in vitro.
- Generation of effector CTL populations.
- Assays for cytotoxic activity against "altered-self" and allogeneic target cells.
- Cold target competition experiments to assess receptor usage.
Main Results:
- CTLs immunized against "altered-self" targets showed high lysis of the immunizing target.
- A low percentage (approximately 1%) of cross-reactive lysis was observed against allogeneic targets differing only at the H-2 haplotype.
- Repeated in vitro stimulation with allogeneic cells enriched for CTLs that lysed both "altered-self" and allogeneic targets with equal efficiency.
- Cold target competition indicated that the same killer cell could lyse both types of targets.
Conclusions:
- Cytotoxic T lymphocytes generated against "altered-self" antigens exhibit cross-reactivity towards allogeneic targets.
- The findings suggest a potential overlap in the recognition mechanisms for "altered-self" and alloreactive CTLs.
- Further investigation is needed to confirm if identical receptors are used for recognizing "altered-self" and foreign H-2 antigens.
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