A polymer containing a repeating peptide sequence can stimulate T-cell-independent IgG antibody production in vivo.
The immunogenicity of a CD4 peptide sequence 303-315 (V4 domain) was determined for three forms of the peptide: (a) a polymer consisting of repeating peptide units, (b) a peptide linked to a large protein carrier, chicken serum albumin, and (c) unmodified free peptide. Two in vivo systems were used: a T-cell-competent BALB/c mouse and a T-cell-deficient nude mouse. In BALB/c mice the IgG antibody responses to the peptide-CSA conjugate were at least 100-fold greater than the response to the polymer, and the free peptide gave no response. However, in contrast to the normal BALB/c mice, in the nude mice the polymer produced the only significant response. Nude mice immunized with the polymer produced a predominantly IgG response with almost equal amounts of IgG1 and IgG 2a + 2b. This IgG subclass distribution was very similar to that obtained in the BALB/c for the peptide-CSA conjugate. Positive sera from both groups were able to react with immobilized CD4 molecule on Western blots, confirming the specificity of both the T-cell-independent as well as T-cell-dependent response. These results suggest that repeating epitopes on the same peptide polymer molecule may cause cross-linking of antigen-specific immunoglobin receptors on B-cells, and thus behave as a relatively T-cell-independent immunogen which can induce isotype switching.
Hillman
K
K
Division of Virology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Shapira-Nahor
O
O
Blackburn
R
R
Hernandez
D
D
Golding
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000955:Antigens, T-Independent / Q000737:chemistry*; D015153:Blotting, Western; D015704:CD4 Antigens / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008819:Mice, Nude / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011108:Polymers
D000955:Antigens, T-Independent; D015704:CD4 Antigens; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D010446:Peptide Fragments; D011108:Polymers