Recognition of host-membrane antigens in the envelope of measles virions.

Trypsin- and acetone-treated virions from either of two strains of measles virus grown in Vero cells stimulated the production in guinea pigs of (i) virus-specific antibodies to polypeptide (P) of molecular weight 70,000 (70K) and to the portion of the HA spike embedded in the viral envelope, but not to M protein, and (ii) antibodies to two host cell membrane antigens which were identified as glycoproteins with molecular weights of 108K and 104K. These host cell antigens were present in increased amounts in infected cells and were intimately associated with the virus. Untreated measles virions grown in Vero cells also stimulated the production of antibody to the 108K glycoprotein. The host polypeptides were less antigenic in virus derived from HEp2 cells, which apparently contained less of these antigens.

Immunological control of Epstein-Barr virus-transformed lymphocytes in multiple sclerosis.

T-cell control of Epstein-Barr virus (EBV)-infected autologous lymphocytes was examined in 25 multiple sclerosis (MS) patients and in 25 healthy individuals, all seropositive for EBV. By assessing regression of cell transformation, 17 patients and all healthy subjects were scored as "regressors." Eight MS patients proved to be "nonregressors," indicating loss of cytotoxic T-cell control. In this group there was apparently a concurrent fall in the mean titer of antibody to Epstein-Barr nuclear antigen.

Immunoelectron microscopic studies on haemagglutinin and haemolysin of measles virus in infected HEp2 cells.

The antigenic determinants of the haemagglutinin and haemolysin antigens of measles virus were located at the surface of HEp2 cells infected with measles virus and on measles virions released from these cells, using immunoelectron microscopy. Antisera specific for haemagglutinin or haemolysin antigen and peroxidase-conjugated antiglobulin were used. Treatment of the infected cells with trypsin removed the virus spikes and prevented binding by the anti-haemagglutinin serum, while the reaction with anti-haemolysin serum was unaltered. This suggests that the antigenic determinants for measles haemagglutinin reside on the spike, while the antigenic determinants for haemolysin reside on, or are close to, the virus membrane.

Increased tendency to spontaneous in-vitro lymphocyte transformation in clinically active multiple sclerosis.

Lymphocytes from 8 of 10 patients with clinically active multiple sclerosis (MS) but from only 3 of 18 patients with quiescent MS and 4 of 20 healthy donors transformed spontaneously on in-vitro culture. The transformed cells from all donors had the characteristics of B lymphocytes (surface and intracytoplasmic immunoglobulin and complement receptors) and carried antigens of Epstein-Barr virus. It is suggested that these results are further evidence that immunoregulation in active MS is abnormal.

The sensitivity of measles virus haemolysin to acetone and the preparation of mono-specific human anti-haemolysin by absorption.

The haemolysin of measles virus, either in the virion or in infected cells, is functionally and antigenically sensitive to acetone. Absorption of human sera with acetone-treated, measles virus-infected cells removes antibodies to all measles virus structural antigens except haemolysin. The antibody titres of absorbed sera give good correlation in HLI, neutralization and fluorescent antibody staining on unfixed infected cells.

Measles virus-specific antibodies and immunoglobulin M antiglobulin in sera from multiple sclerosis and rheumatoid arthritis patients.

When rheumatoid factor in rheumatoid arthritis and multiple sclerosis sera was titrated by the fluorescent antibody method on measles virus-infected cells, there was a marked and variable drop in titer on acetone-fixed cells as compared with unfixed cells. This was accounted for by the failure of measles virus hemolysin-inhibiting (HLI) antibody of the immunoglobulin G class to bind to acetone-fixed infected cells. It was shown by staining unfixed and acetone-fixed measles virus-infected cells that rheumatoid factor in most rheumatoid arthritis sera combined with measles virus-specific hemagglutinin-inhibiting and HLI antibodies, whereas rheumatoid factor in multiple sclerosis sera combined only with HLI antibody. Rheumatoid factor of similar specificity was also observed in normal sera and occasionally in rheumatoid arthritis sera. Both rheumatoid arthritis and multiple sclerosis sera showed almost identical increases in average titer above normal of measles virus-specific fluorescent staining immunoglobulin G and HLI antibodies.

Affinity for measles virus anti-haemolysin of a residual immunoglobulin M in sera of some patients with multiple sclerosis.

HEp2 cells persistently infected with measles virus were treated with trypsin to remove haemagglutinin (HA) and examined unfixed or fixed in acetone by fluorescent antibody methods, comparing those sera specific for structural antigens of the virus. Staining patterns combined with the blocking of specific immunofluorescence indicated that IgG specific for measles virus haemolysin could be recognized in multiple sclerosis (MS) sera and that in some sera from which rheumatoid factor had been removed, a residual IgM (MS-IgM) was absorbed to measles virus-infected cells and showed the same specificity in blocking tests as measles virus anti-haemolysin. MS-IgM could be removed from sera by absorption with latex particles coated with human IgG and would seem to be anti-globulin with preferential affinity for anti-haemolysin.

Measles and other virus-specific immunoglobulins in multiple sclerosis.

Immunoglobulins M and G specific for meales, herpes simplex, and rubella viruses were assayed by the fluorescent antibody method in sera and cerebrospinal fluids (C.S.F.) obtained simultaneously from 30 patients with multiple sclerosis, 30 patients with other neurological diseases, and 30 "normal" control subjects. Sera of 11 out of 30 patients with multiple sclerosis had IgM which reacted specifically with measles virus-infected cells, compared with 2 out of 30 of the patients with other neurological diseases and none of the 30 normal controls. Virus-specific IgM was not found in C.S.F. by this method.The geometric mean titre of measles virus-specific IgG in serum was significantly higher in the multiple sclerosis group than in either control group, and while IgG specific for all three viruses was found in C.S.F., suggesting transfer across the blood-brain barrier, measles IgG predominated.