Summary Activation of CD 4 + T cells helps to establish and maintain immune responses. During infection with lymphocytic choriomeningitis virus ( LCMV ) clone 13, the CD 4 + T‐cell responses are lost. In this study, we were interested in the nature of the CD 4 + T‐cell responses following infection with LCMV clone 13. To pursue this question, we infected C 57 BL /6 mice with LCMV clone 13. We used a GP 66‐80 MHC C lass II tetramer to determine whether the CD 4 + T cells were present following infection with LCMV clone 13. We determined that the cells were present and antigen specific, but not functional. We attributed their dysfunction to the presence of CD 4 + T‐cell inhibitory ligands. We further stained for the presence of CD 4 + T‐cell inhibitory ligands. We found that the during chronic infection the number of CD 4 + T cells expressing programmed death‐1 and CD 160 were greater over the time–course study than the other CD 4 + T‐cell inhibitory ligands. These data show that using CD 4 + T ‐cell inhibitory ligands as a reagent for characterization can help in understanding the complex immune responses associated with persistent infections.