Streptococcal M1 Protein Research Articles

Nucleotide substitutions and small‐scale insertion produce size and antigenic variation in group A streptococcal M1 protein

The presence of M protein on the surface of group A streptococci (GAS) confers the ability of the cell to resist phagocytosis in the absence of type-specific antibodies. It undergoes antigenic variation with more than 80 different serotypes having been defined. We have sequenced the M protein gene (emm1.1) from strain CS190 and present evidence that individual nucleotide substitutions are responsible for sequence variation in the N-terminal non-repeat region of emm1.1 and these substitutions have altered antibody recognition of opsonic epitopes. The N-terminal non-repeat domains of two other closely related strains, 71-155 and 76-088, were found to have sequence identical to emm1.1 with the addition of a 21 bp insert. This study provides the first evidence that nucleotide substitutions and small insertions are responsible for size and antigenic variation in the N-terminal non-repeat domain of the M protein of GAS.

A Secreted Receptor Related to M1 Protein of Streptococcus pyogenes Binds to Fibrinogen, IgG, and Albumin

An extracellular protein (eMP) of Streptococcus pyogenes M type 1 was isolated by affinity chromatography on albumin- and IgG-Sepharose. The protein was found to bind to the human plasma proteins, fibrinogen, IgG, and albumin. Analysis of eMP by Western blotting demonstrated a major band with a molecular weight of 49 kD which was responsible for binding of the three plasma proteins. The purified protein was found to bind selectively to human and primate polyclonal IgG, human and mouse albumin, as well as human fibrinogen which has been the only fibrinogen tested. Serological investigations revealed a close relation of eMP to streptococcal M1 protein. It showed a reaction of identity with cell-extracted M1 protein in immunodiffusion. Moreover, the 49 kD peptide responsible for binding, was recognized with an antiserum directed against the 20 amino acids comprising synthetic peptide (42VAL-61GLU) of the N-terminal part of the M1 protein sequence. The affinity of M protein to plasma proteins other than fibrinogen opens new approaches to its purification by affinity chromatography.

Stimulation of Lymphocyte Transformation by Streptococcal Type M1 Protein: Relationship to HL-A Antigens

Abstract M1 protein isolated from group A streptococci, type 1, stimulates human peripheral blood lymphocytes in short-term tissue culture to undergo a dose-dependent increase in DNA synthesis. The degree of this lymphocyte stimulation is not related either to HL-A phenotype, the serum anti-M1 titer of the lymphocyte donor, or the effectiveness of M1 antigen in blocking the cytotoxic activity of HL-A alloantisera. However, both HL-A allo- and heteroantisera are highly effective in specifically inhibiting M1 mitogenic activity. This inhibitory effect clearly depends on anti-HL-A antibody since HL-A alloantisera are rendered ineffective when specifically absorbed with cultured human lymphoid cells. The mechanism by which anti-HL-A antibodies suppress the M1-induced lymphocyte transformation is thought to involve a masking of the M1 protein's mitogenic site such as to prevent interactions with specific lymphocyte receptors required for induction of the proliferative response.