Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation

Immunity. 2016 May 17;44(5):989-1004. doi: 10.1016/j.immuni.2016.05.001.


Co-inhibitory receptors, such as CTLA-4 and PD-1, have an important role in regulating T cell responses and have proven to be effective targets in the setting of chronic diseases where constitutive co-inhibitory receptor expression on T cells dampens effector T cell responses. Unfortunately, many patients still fail to respond to therapies that target CTLA-4 and PD-1. The next wave of co-inhibitory receptor targets that are being explored in clinical trials include Lag-3, Tim-3, and TIGIT. These receptors, although they belong to the same class of receptors as PD-1 and CTLA-4, exhibit unique functions, especially at tissue sites where they regulate distinct aspects of immunity. Increased understanding of the specialized functions of these receptors will inform the rational application of therapies that target these receptors to the clinic.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • CTLA-4 Antigen / metabolism
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Humans
  • Immune Tolerance*
  • Lymphocyte Activation
  • Lymphocyte Activation Gene 3 Protein
  • Programmed Cell Death 1 Receptor / metabolism
  • Receptor Cross-Talk
  • Receptors, Immunologic / metabolism*
  • Signal Transduction
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • CTLA-4 Antigen
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic
  • TIGIT protein, human
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human