HIV infection--induced posttranslational modification of T cell signaling molecules associated with disease progression.
In attempt to elucidate the mechanism of the HIV infection induced T cell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individuals. Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and ZAP-70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic/AIDS patients as well as in T cells of individuals in acute and early asymptomatic stages of HIV infection. Unexpectedly, the detection of Lck, Fyn, and ZAP-70 was reversed after the treatment of cell lysates with dithiothreitol. This suggests that PTKs Lck, Fyn, and ZAP-70 were modified by a mechanism altering the status of sulfhydryl groups. Moreover, this mechanism seems to affect selectively T cells of HIV infected patients since B cell PTKs Syk and Lyn were detected structurally and functionally intact. Interestingly, similar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals. Modification of T cell PTKs may thus underlie the HIV-induced impairment of lymphocyte function and may potentially predict disease progression.
Stefanová
I
I
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. IStefanova@pop.niaid.nih.gov
Saville
M W
MW
Peters
C
C
Cleghorn
F R
FR
Schwartz
D
D
Venzon
D J
DJ
Weinhold
K J
KJ
Jack
N
N
Bartholomew
C
C
Blattner
W A
WA
Yarchoan
R
R
Bolen
J B
JB
Horak
I D
ID
D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D015151:Immunoblotting; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000276:immunology; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D051746:ZAP-70 Protein-Tyrosine Kinase; D019061:src-Family Kinases / Q000032:analysis / Q000276:immunology
D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013438:Sulfhydryl Compounds; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D019061:src-Family Kinases