Lymphocyte Function-Associated Antigens: Regulation of Lymphocyte Adhesions in Vitro and Immunity in Vivo

  • Eric Martz
  • Stanislaw H. Gromkowski
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 187)


Antibodies to most cytolytic T lymphocyte (CTL) external membrane antigens have no effect on CTL-mediated killing in the absence of complement. However, antibodies which do inhibit killing have now been identified for 7 distinct molecular sites. Antibodies to 6 of these “lymphocyte function-associated antigens” (LFAs, also called “blocking sites”) inhibit when bound to the CTL, and to the 7th, when bound to the target cell. Mouse homologs have been identified for only 4 of the 7 human LFAs. 5 (probably 6) of the blocking sites inhibit by interfering with adhesion formation between the CTL and the target cell; the exception is T3. None of the presently identified blocking sites are believed to be lethal hit structures (CTL “toxin”).

Reduction of target cell H-2 alloantigen density by pretreatment with papain reduces CTL-target functional “affinity”, and increases susceptibility to inhibition 100-fold for anti-Lyt- 2,3 and 10-fold for anti-LFA-1. This is consistent with the hypothesis that Lyt-2,3 aids in recognition of class 1 MHC antigens, perhaps by strengthening intercellular adhesion.

On the other hand, LFA-1 appears to function differently. Trypsin pretreatment of target cells has little effect on MHC antigens or CTL-target affinity, yet still increases by 10-fold susceptibility to inhibition by anti-LFA-1. This is seen in both

human and mouse CTL systems. These results suggest the existence of a non-MHC target structure which participates in the adhesion- strengthening function of LFA-1, and which is trypsin (and papain) sensitive: the “trypsin-sensitive counter blocker” (TSCB). LFA-3 may be the human TSCB.

The roles of these LFAs in intercellular adhesion extend to more general cell adhesions. Anti-LFA-1 and ainti-LFA-3 weaken the spontaneous adhesions which form between cells of the human B cell line JY. These homotypic adhesions are not initiated by immunologic recognition.

Anti-LFA-1 is more potent at prolonging allograft survival in vivo than are anti-Lyt-2,3, anti-T200, anti-Thy-1, or anti-I-A. Thus, the potent anti-adhesion properties of LFA-1 seen in vitro may lead to useful immunotherapy in the clinic.


Target Cell Blocking Site Immunologic Recognition Bean Trypsin Inhibitor Homotypic Adhesion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Eric Martz
    • 1
  • Stanislaw H. Gromkowski
    • 1
  1. 1.Department of MicrobiologyUniversity of MassachusettsAmherstUSA

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